Animal Models Of Eating Disorders 1st Edition

Sarah Shafer Berger Phd download

https://ebookbell.com/product/animal-models-of-eating-
disorders-1st-edition-sarah-shafer-berger-phd-4290498

Explore and download more ebooks at ebookbell.com

Here are some recommended products that we believe you will be
interested in. You can click the link to download.

Animal Models Of Eating Disorders 2nd Ed Nicole M Avena

https://ebookbell.com/product/animal-models-of-eating-disorders-2nd-
ed-nicole-m-avena-22417362

Animal Models Disorders Of Eating Behaviour And Body Composition 1st

Edition Molly S Bray

https://ebookbell.com/product/animal-models-disorders-of-eating-
behaviour-and-body-composition-1st-edition-molly-s-bray-4284972

Animal Models Of Diabetes 1st Aileen J F King

https://ebookbell.com/product/animal-models-of-diabetes-1st-aileen-j-
f-king-47710556

Animal Models Of Reproductive Behavior 1st Edition Ral G Paredes

https://ebookbell.com/product/animal-models-of-reproductive-
behavior-1st-edition-ral-g-paredes-50176988
Animal Models Of Epilepsy Methods And Innovations Neuromethods 40
2009th Edition Scott C Baraban Ed

https://ebookbell.com/product/animal-models-of-epilepsy-methods-and-
innovations-neuromethods-40-2009th-edition-scott-c-baraban-ed-55063456

Animal Models Of Movement Disorders Mark Ledoux Editor

https://ebookbell.com/product/animal-models-of-movement-disorders-
mark-ledoux-editor-2160110

Animal Models Of Tcell Mediated Skin Diseases Ernst Schering Research

Foundation Workshop 50 1st Edition T Zollner Editor

https://ebookbell.com/product/animal-models-of-tcell-mediated-skin-
diseases-ernst-schering-research-foundation-workshop-50-1st-edition-t-
zollner-editor-2164280

Animal Models Of Diabetes Frontiers In Research 2nd Edition Eleazar

Shafrir

https://ebookbell.com/product/animal-models-of-diabetes-frontiers-in-
research-2nd-edition-eleazar-shafrir-2193802

Animal Models Of Human Disease Volume 100 Molecular Biology And

Translational Science 1st Edition Min Kyungtai

https://ebookbell.com/product/animal-models-of-human-disease-
volume-100-molecular-biology-and-translational-science-1st-edition-
min-kyungtai-2362602
NEUROMETHODS

Series Editor
Wolfgang Walz
University of Saskatchewan
Saskatoon, SK, Canada

For further volumes:

http://www.springer.com/series/7657
Animal Models of Eating
Disorders

Edited by

Nicole M. Avena
Department of Psychiatry, University of Florida, Gainesville, FL, USA
Editor
Nicole M. Avena
Department of Psychiatry
University of Florida
Gainesville, FL, USA

ISSN 0893-2336 ISSN 1940-6045 (electronic)

ISBN 978-1-62703-103-5 ISBN 978-1-62703-104-2 (eBook)
DOI 10.1007/978-1-62703-104-2
Springer Totowa Heidelberg New York Dordrecht London

Library of Congress Control Number: 2012947378

© Springer Science+Business Media, LLC 2013

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is
concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction
on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this
legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for
the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.
Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the
Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions
for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution
under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not
imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of publication, neither
the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be
made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper

Cover image designed by Jedediah Smith

Humana Press is a brand of Springer

Springer is part of Springer Science+Business Media (www.springer.com)
Foreword

The salient features of the most common human eating disorders are simple to describe
and, in practice, not difficult to recognize. The relentless pursuit of thinness accomplished
by severe calorie restriction and, often, increased physical activity are the hallmark features
of anorexia nervosa, and are unchanged since the syndrome was first clearly described well
over 100 years ago. More recently, clinicians have come to appreciate the syndromes of
bulimia nervosa and binge eating disorder, both of which are characterized by the recurrent
occurrence of binge eating. These patterns of eating behaviors are clearly abnormal and are
sufficiently robust that they have been examined objectively in laboratory studies. However,
it has proven exceedingly difficult to understand precisely how these disturbing behaviors
arise, and, once they have become established, why they are frequently so persistent. These
questions are among the most important facing clinical researchers in this field.
In many areas of medicine, it has been possible to examine critical features of illnesses
in animal models. For example, mechanisms underlying the development of inflammatory
diseases, cardiovascular illnesses, and malignancies have been successfully probed in nonhu-
man species, and such investigations have led to major advances in understanding critical
pathological processes and to the development of effective treatments. The development of
animal models to study mental disorders has been much more difficult, as these disorders
usually involve cognitive and emotional disturbances that are extremely difficult to
confidently express in animals. In recent decades, however, significant progress has been
made in probing the neural circuitry of disturbances, which may be critical to understand-
ing mental disorders. For example, the mechanisms responsible for fear learning and avoid-
ance behavior in animals may be of substantial relevance to the pathophysiology of anxiety
disorders in humans. Similarly, disturbances of working memory, the function of which can
be elegantly probed in animals, may play an important role in the functional impairment of
individuals with schizophrenia.
The current volume is a testament to the burgeoning use of animal models to probe
core facets of human eating disorders. Part I focuses on binge eating, the salient feature of
both bulimia nervosa and binge eating disorder. The chapters in this section usefully
describe a range of methods by which animals can be induced to engage in behavior that
resembles the binge eating of individuals with eating disorders. Methods include simply
making palatable foods available in the environment, restricting access to such foods,
increasing the level of stress, and requiring operant behavior to obtain access to palatable
foods. Such manipulations have clear parallels to the impact of external parameters and of
internal emotion state on the fluctuation of symptoms in human eating disorders. In addi-
tion, several chapters highlight how the potential utility of medication can be explored in
such models. The section also includes a chapter describing the direct translation of sham
feeding, a very useful procedure to examine the control of animal eating behavior, to
humans with eating disorders. In addition, deep-brain stimulation in a binge eating model
is discussed.

v
vi Foreword

Part I also explores a long-standing and controversial area in human eating disorders,
namely, the significance of the striking parallels between eating disorders and addictions.
With impressive frequency and conviction, individuals with binge eating describe their
struggles with food in remarkably similar terms to those used by individuals who struggle
with drugs of abuse. Chapters in this section describe complementary approaches to exam-
ining this issue, including changes in behavior and in dopamine signaling associated with
binge eating of sugar, the relationship between saccharin preference and vulnerability to
drug abuse, and the persistence of food-seeking despite aversive consequences. Attempts to
elucidate the parallels between eating disorders and substance abuse by focusing purely on
descriptive human studies have yielded limited clarity, and the attempt to bring insights
from animal models is most welcome.
The self-imposed food restriction that is the salient feature of anorexia nervosa is chal-
lenging to study both in humans and animals. Part II of this volume is comprised of chap-
ters describing a range of innovative approaches which may provide insights into this striking
behavioral syndrome. Several of the chapters address the circumstances and controls of
increased physical activity which, under certain experimental conditions, become so marked
that weight loss is life-threatening. Other chapters probe the contributions of genetic fac-
tors and neurotransmitters on reduced food intake and the effect of weight loss on the
functioning of the reward system.
Part II of this volume also focuses on the critical issue of development. Almost all cases
of anorexia nervosa and bulimia nervosa begin during adolescence. While adolescence is a
time of enormous psychological and biological change and stress, whether and how such
factors contribute to the vulnerability to develop eating disorders is unknown. The chapters
in this section identify behavioral and biological parameters and the impact of stress during
early development that may set the stage for the development of eating disorders.
In summary, this volume brings together a range of valuable perspectives on how
aspects of animal eating behavior can be manipulated to resemble key features of human
eating disorders, and thereby provide provocative insights into the factors that facilitate the
development and persistence of disturbed eating in humans. This line of research is a most
welcome new addition to the attempts to decipher the mysteries of anorexia nervosa, buli-
mia nervosa, and binge eating.

New York, NY, USA B. Timothy Walsh M.D.

Preface to the Series

Under the guidance of its founders Alan Boulton and Glen Baker, the Neuromethods series
by Humana Press has been very successful since the first volume appeared in 1985. In about
17 years, 37 volumes have been published. In 2006, Springer Science + Business Media
made a renewed commitment to this series. The new program will focus on methods that
are either unique to the nervous system and excitable cells or which need special consider-
ation to be applied to the neurosciences. The program will strike a balance between recent
and exciting developments like those concerning new animal models of disease, imaging,
in vivo methods, and more established techniques. These include immunocytochemistry
and electrophysiological technologies. New trainees in neurosciences still need a sound
footing in these older methods in order to apply a critical approach to their results. The
careful application of methods is probably the most important step in the process of scientific
inquiry. In the past, new methodologies led the way in developing new disciplines in the
biological and medical sciences. For example, Physiology emerged out of Anatomy in the
nineteenth century by harnessing new methods based on the newly discovered phenome-
non of electricity. Nowadays, the relationships between disciplines and methods are more
complex. Methods are now widely shared between disciplines and research areas. New
developments in electronic publishing also make it possible for scientists to download chap-
ters or protocols selectively within a very short time of encountering them. This new
approach has been taken into account in the design of individual volumes and chapters in
this series.

Wolfgang Walz

vii
Preface

This volume of the series Neuromethods provides an in-depth review of preclinical labora-
tory animal models used in the study of eating disorders. The prevalence of eating disorders
in the U.S. and in other developed countries continues to pose a problem, and clinicians
continue to struggle with treating these disorders of complex etiologies. Many researchers
turn to the use of animal models to assist in their investigation and characterization of the
behaviors and neurochemical alterations associated with them. As such, animal models have
become integral to understanding the biological basis of eating disorders. This volume
consists of chapters contributed by experts in the field who are well versed in the develop-
ment and implementation of these models.
The study of eating disorders is a burgeoning field. In recent years, there have been
many new discoveries and theories on their biological bases. The growth of the field has led
to a vast array of empirical articles on the study of eating disorders, and the development of
new models that can be used to study these disorders continues to stimulate new research.
This book serves as a collection of detailed techniques that scientists can follow. Since eat-
ing disorders are complex and likely due to a combination of environmental, genetic, and
social causes, the following chapters have been designed to highlight different contributing
factors. Collectively, these chapters give a comprehensive and representative overview of
both recently developed and classic methodologies used in the study of eating disorders.
Gratitude is extended to all of the contributing authors for their hard work and excel-
lent chapters. I would also like to thank Ms. Cindy Kroll for her invaluable editorial assis-
tance, as well as Ms. Miaoyuan (May) Wang for her assistance with the images and Ms.
Susan Murray, Monica Gordillo and Hana Shin for their help with formatting and editing.
I would also like to thank Wolfgang Walz (Series Editor) and Springer for their guidance
and interest in this important topic.

Gainesville, FL, USA Nicole M. Avena

ix
Contents

Foreword. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Preface to the Series. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

PART I BINGE EATING, BULIMIA, AND HEDONIC OVEREATING

1 Introduction: Binge Eating, Bulimia Nervosa,
and Hedonic Overeating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Sarah Shafer Berger and Marian Tanofsky-Kraff
2 Binge-Prone Versus Binge-Resistant Rats and Their Concomitant
Behavioral Profiles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Mary M. Boggiano
3 Binge Eating in Female Rats Induced by Yo-Yo Dieting and Stress . . . . . . . . . 27
Carlo Cifani, Maria Vittoria Micioni Di Bonaventura,
Roberto Ciccocioppo, and Maurizio Massi
4 Binge-Type Eating Induced by Limited Access to Optional Foods. . . . . . . . . . 51
Rebecca L.W. Corwin and Francis H.E. Wojnicki
5 Assessment of Stress-Independent Binge-Like Eating Behavior in Mice . . . . . . 69
Traci A. Czyzyk, Jesline Alexander-Chacko, Joelle Dill,
Dana K. Sindelar, and Michael A. Statnick
6 Predicting and Classifying Rats Prone to Overeating Fat . . . . . . . . . . . . . . . . . 83
Irene Morganstern, Jessica R. Barson, and Sarah F. Leibowitz
7 Modeling Binge Eating in Nonhuman Primates. . . . . . . . . . . . . . . . . . . . . . . . 97
Richard W. Foltin
8 Psychosocial Stress and Diet History Promote Emotional
Feeding in Female Rhesus Monkeys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Vasiliki Michopoulos, Carla Moore, and Mark E. Wilson
9 Stressful Experiences in Early Life and Subsequent Food Intake. . . . . . . . . . . . 127
Jeong Won Jahng
10 Sham Feeding in Rats Translates into Modified Sham Feeding
in Women with Bulimia Nervosa and Purging . . . . . . . . . . . . . . . . . . . . . . . . . 155
Diane A. Klein and Gerard P. Smith
11 Animal Models of Binge Eating Palatable Foods:
Emergence of Addiction-Like Behaviors
and Brain Changes in the Rat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Miriam E. Bocarsly and Nicole M. Avena

xi
xii Contents

12 Deep Brain Stimulation for the Treatment of Binge Eating:

Mechanisms and Preclinical Models. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Casey H. Halpern, Mark Attiah, and Tracy L. Bale
13 Saccharin Preference in Rats: Relation to Impulsivity and Drug Abuse. . . . . . . 201
Marilyn E. Carroll, Nathan A. Holtz, and Natalie E. Zlebnik
14 Food Seeking in Spite of Harmful Consequences. . . . . . . . . . . . . . . . . . . . . . . 235
Rossella Ventura, Emanuele Claudio Latagliata,
Enrico Patrono, Matteo Di Segni, and Stefano Puglisi-Allegra

PART II ANOREXIA AND UNDEREATING

15 Introduction: Anorexia and Undereating. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257

Guido K.W. Frank
16 Food Restriction and Reward in Rats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Kenneth D. Carr and Soledad Cabeza de Vaca
17 Activity-Based Anorexia in the Rat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Nicole C. Barbarich-Marsteller
18 Food-Anticipatory Activity: Rat Models and Underlying Mechanisms . . . . . . . 291
Myrte Merkestein, Linda A.W. Verhagen, and Roger A.H. Adan
19 Anorexia and Drugs of Abuse Abnormally Suppress Appetite,
the Result of a Shared Molecular Signal Foul-Up . . . . . . . . . . . . . . . . . . . . . . 319
Laetitia Laurent, Alexandra Jean, Christine Manrique,
Mohamed Najimi, Fatiha Chigr, and Valérie Compan
20 The Anorectic Phenotype of the anx/anx Mouse
Is Related to Hypothalamic Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Ida A.K. Nilsson, Charlotte Lindfors, Tomas Hökfelt,
Martin Schalling, and Jeanette E. Johansen
21 Functional Magnetic Resonance Imaging in Awake Rats:
Studies Relevant to Addiction and the Reward Circuitry . . . . . . . . . . . . . . . . . 351
Marcelo Febo
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
Contributors

ROGER A.H. ADAN, PH.D. • Department of Neuroscience and Pharmacology,

Rudolf Magnus Institute of Neuroscience, University Medical Centre,
Utrecht, The Netherlands
JESLINE ALEXANDER-CHACKO • Lilly Research Laboratories, Eli Lilly and Company,
Indianapolis, IN, USA
MARK ATTIAH • Department of Animal Biology, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA, USA
NICOLE M. AVENA, PH.D. • Department of Psychiatry, University of Florida,
Gainesville, FL, USA
TRACY L. BALE, PH.D. • School of Veterinary Medicine, University of Pennsylvania,
Philadelphia, PA, USA
NICOLE C. BARBARICH-MARSTELLER, PH.D. • College of Physicians and Surgeons,
Columbia University, New York, NY, USA
JESSICA R. BARSON, PH.D. • Laboratory of Behavioral Neurobiology, The Rockefeller
University, New York, NY, USA
SARAH SHAFER BERGER, PH.D. • Department of Medical and Clinical Psychology,
Uniformed Services University of the Health Sciences and Section on Growth
and Obesity, Program in Developmental Endocrinology and Genetics,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD, USA
MIRIAM E. BOCARSLY • Department of Psychology and Program in Neuroscience,
Princeton University, Princeton, NJ, USA
MARY M. BOGGIANO, PH.D. • Department of Psychology, Behavioral Neuroscience
Division, University of Alabama, Birmingham, AL, USA
KENNETH D. CARR, PH.D. • Departments of Psychiatry, Molecular Pharmacology and
Biochemistry, New York University Langone Medical Center, New York, NY, USA
MARILYN E. CARROLL, PH.D. • Department of Psychiatry, University of Minnesota,
Minneapolis, MN, USA
FATIHA CHIGR, PH.D. • Laboratoire Génie Biologique, FST, Université Sultan
Moulay Slimane, Beni-Mellal, Morocco
ROBERTO CICCOCIOPPO, PH.D. • School of Pharmacy, Pharmacology Unit,
University of Camerino, Camerino, Italy
CARLO CIFANI, PH.D. • School of Pharmacy, Pharmacology Unit,
University of Camerino, Camerino, Italy

xiii
xiv Contributors

VALÉRIE COMPAN, PH.D. • Département de Neurobiologie, Centre National de la

Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 5203,
Institut National de la Santé et de la Recherche Médicale, U661,
Université Montpellier I and II, Institut de Génomique Fonctionnelle,
Université de Nîmes, Montpellier, France
REBECCA L.W. CORWIN, PH.D. • Nutritional Sciences Department, College of Health
and Human Development, The Pennsylvania State University, University Park,
PA, USA
TRACI A. CZYZYK, PH.D. • Department of Physiology, Mayo Clinic Arizona, Scottsdale,
AZ, USA
SOLEDAD CABEZA DE VACA, PH.D. • Department of Psychiatry, New York University
Langone Medical Center, New York, NY, USA
MARIA VITTORIA MICIONI DI BONAVENTURA • School of Pharmacy, Pharmacology Unit,
University of Camerino, Camerino, Italy
MATTEO DI SEGNI • Santa Lucia Foundation, European Centre for Brain Research
(CERC), Roma, Italy; Dipartimento di Psicologia and Centro “Daniel Bovet”,
University “La Sapienza”, Roma, Italy
JOELLE DILL • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis,
IN, USA
MARCELO FEBO, PH.D. • Department of Psychiatry, University of Florida,
Gainesville, FL, USA
RICHARD W. FOLTIN, PH.D. • Division on Substance Abuse, New York State Psychiatric
Institute and Department of Psychiatry, College of Physicians and Surgeons
of Columbia University, New York, NY, USA
GUIDO K.W. FRANK, M.D. • University of Colorado Anschutz Medical Campus,
Children’s Hospital Colorado, Aurora, CO, USA
CASEY H. HALPERN, M.D. • Department of Neurosurgery, University of Pennsylvania,
Philadelphia, PA, USA
TOMAS HÖKFELT, M.D., PH.D. • Department of Neuroscience, Karolinska Institutet,
Stockholm, Sweden
NATHAN A. HOLTZ • Department of Psychiatry, University of Minnesota,
Minneapolis, MN, USA
JEONG WON JAHNG, PH.D. • School of Dentistry, Seoul National University,
Seoul, South Korea
ALEXANDRA JEAN, PH.D. • Département de Neurobiologie, Centre National de la
Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 5203,
Institut National de la Santé et de la Recherche Médicale, U661,
Université Montpellier I and II, Institut de Génomique Fonctionnelle,
Université de Nîmes, Montpellier, France
JEANETTE E. JOHANSEN, PH.D. • Department of Molecular Medicine and Surgery,
Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine,
Karolinska University Hospital, Stockholm, Sweden
DIANE A. KLEIN, M.D. • College of Physicians & Surgeons, Columbia University,
New York, NY, USA
EMANUELE CLAUDIO LATAGLIATA, PH.D. • Santa Lucia Foundation, European Centre
for Brain Research (CERC), Roma, Italy; Dipartimento di Psicologia
and Centro “Daniel Bovet”, University “La Sapienza”, Roma, Italy
 Contributors xv

LAETITIA LAURENT, PH.D. • Département de Neurobiologie, Centre National de la

Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 5203,
Institut National de la Santé et de la Recherche Médicale, U661,
Université Montpellier I and II, Institut de Génomique Fonctionnelle,
Université de Nîmes, Montpellier, France
SARAH F. LEIBOWITZ, PH.D. • Laboratory of Behavioral Neurobiology,
The Rockefeller University, New York, NY, USA
CHARLOTTE LINDFORS • Department of Molecular Medicine and Surgery,
Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine,
Karolinska University Hospital, Stockholm, Sweden
CHRISTINE MANRIQUE, PH.D. • CNRS, Neurobiologie Intégrative et Adaptative,
Université Aix-Marseille I, Marseille, France
MAURIZIO MASSI, PH.D. • School of Pharmacy, Pharmacology Unit, University of Cam-
erino, Camerino, Italy
MYRTE MERKESTEIN, PH.D. • Department of Neuroscience and Pharmacology,
Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht,
The Netherlands
VASILIKI MICHOPOULOS • Development & Cognitive Neuroscience, Yerkes National
Primate Research Center, Emory University, Atlanta, GA, USA
CARLA MOORE • Development & Cognitive Neuroscience, Yerkes National Primate
Research Center, Emory University, Atlanta, GA, USA
IRENE MORGANSTERN, PH.D. • Laboratory of Behavioral Neurobiology, The Rockefeller
University, New York, NY, USA
MOHAMED NAJIMI, PH.D. • Laboratoire Génie Biologique, FST, Université Sultan Mou-
lay Slimane, Beni-Mellal, Morocco
IDA A.K. NILSSON, PH.D. • Department of Molecular Medicine and Surgery,
Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine,
Karolinska University Hospital, Stockholm, Sweden
ENRICO PATRONO • Dipartimento di Scienze Cliniche Applicate e Biotecnologie,
University of L’Aquila, L’Aquila, Italy
Santa Lucia Foundation, European Centre for Brain Research (CERC),
Roma, Italy
STEFANO PUGLISI-ALLEGRA, PH.D. • Santa Lucia Foundation, European Centre
for Brain Research (CERC), Roma, Italy; Dipartimento di Psicologia and Centro
“Daniel Bovet”, University “La Sapienza”, Roma, Italy
MARTIN SCHALLING, M.D. • Department of Molecular Medicine and Surgery,
Karolinska Institutet, Stockholm, Sweden
DANA K. SINDELAR • Lilly Research Laboratories, Eli Lilly and Company,
Indianapolis, IN, USA
GERARD P. SMITH, M.D. • Department of Psychiatry, Weill Cornell Medical College,
New York, NY, USA
MICHAEL A. STATNICK, PH.D. • Lilly Research Laboratories, Eli Lilly and Company,
Indianapolis, IN, USA
xvi Contributors

MARIAN TANOFSKY-KRAFF, PH.D. • Department of Medical and Clinical Psychology,

Uniformed Services University of the Health Sciences, Bethesda, MD, USA;
Program in Developmental Endocrinology and Genetics, Section on Growth
and Obesity, Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, Bethesda, MD, USA
ROSSELLA VENTURA, PH.D. • Dipartimento di Scienze Cliniche
Applicate e Biotecnologie University of L’Aquila, L’Aquila, Italy
Santa Lucia Foundation, European Centre for Brain Research (CERC),
Roma, Italy
LINDA A.W. VERHAGEN, PH.D. • Department of Mouse Genetics and Metabolism,
Institute for Genetics, University of Cologne, Köln, Germany
B. TIMOTHY WALSH, M.D. • Department of Psychiatry, Columbia University,
New York State Psychiatric Institute, New York, NY, USA
MARK E. WILSON, PH.D. • Development & Cognitive Neuroscience, Yerkes National
Primate Research Center, Emory University, Atlanta, GA, USA
FRANCIS H.E. WOJNICKI, PH.D. • Nutritional Sciences Department, College of Health
and Human Development, The Pennsylvania State University,
University Park, PA, USA
NATALIE E. ZLEBNIK • Department of Psychiatry, University of Minnesota,
Minneapolis, MN, USA
 Part I

Binge Eating, Bulimia, and Hedonic Overeating

 Chapter 1

Introduction: Binge Eating, Bulimia Nervosa,

and Hedonic Overeating
Sarah Shafer Berger and Marian Tanofsky-Kraff

Abstract
Binge eating, bulimia nervosa, and hedonic overeating share a critical common component; namely,
overeating that involves a lack of healthy restraint. However, these constructs are distinct from one another
and are related to differential correlates and outcomes in human beings. Notably, all three behaviors can
be modeled in animals, thus providing important insights to inform human research.

Key words: Overeating, Loss of control, Compensatory behaviors

1. Binge Eating
and Binge Eating
Disorder
Binge eating is characterized by the consumption of an objectively
large amount of food accompanied by a feeling of loss of control
(i.e., the sense that one cannot control what or how much one is
eating) over eating (1). Binge eating is the hallmark behavior of
binge-eating disorder (BED). BED is defined as recurrent episodes
of binge eating with associated impairment and/or distress regard-
ing the eating episodes (1). The prevalence of BED is estimated to
be about 3% with the disorder being somewhat more prevalent in
women (2). It is estimated that 76% of adults and 85% of adoles-
cents with BED also have psychiatric comorbidities (e.g., anxiety,
mood disorders, substance abuse) (2, 3) or suicidal ideation (3).
Functional impairment in work, home, or personal life is also
reported among individuals with BED compared to non-obese
individuals without BED (2).
Approximately 35% of those who regularly binge eat are over-
weight or obese (2) and may be at higher risk for hypertension,
dyslipidemia, or type 2 diabetes (4–7). However, individuals with
BED differ from obese adults without the disorder. In laboratory

Nicole M. Avena (ed.), Animal Models of Eating Disorders, Neuromethods, vol. 74,
DOI 10.1007/978-1-62703-104-2_1, © Springer Science+Business Media, LLC 2013

3
4 S.S. Berger and M. Tanofsky-Kraff

investigations of eating and studies using self-report surveys,

individuals with BED consume significantly more total energy
than obese adults without BED (8–12). During weight loss treat-
ment, some studies show less weight loss, more rapid weight
regain, or more attrition from treatment for those individuals
with BED compared to individuals without BED (8, 13).

2. Bulimia Nervosa

Similar to BED, bulimia nervosa involves recurrent binge eating,

impairment, and/or distress. However, bulimia nervosa also
involves compensatory behaviors (e.g., vomiting, laxative use,
excessive exercise) following binge episodes in order to prevent
weight gain (1). The rates of bulimia nervosa are estimated to be
lower than BED, with 1.5% of women and 0.5% of men reporting
lifetime prevalence (2). Bulimia nervosa is associated with psychi-
atric comorbidities like suicidal ideation (53% reported ideation
and 35% reporting attempts) and functional impairment (2, 3).
Unlike BED, there are associated features that differ; individuals
with bulimia nervosa tend to eat fewer meals, nibble more, and
have higher levels of dietary restraint (14). Persistent bulimia ner-
vosa is associated with body image disturbances, general psychopa-
thology, and impaired sexuality and social relationships (15).

3. Hedonic
Overeating
Hedonic overeating is the over consumption of highly palatable
foods in the absence of current energy needs (16). It is often dis-
cussed in the context of food addiction (17), which remains a con-
troversial topic (18). Nevertheless, hedonic overeating may be an
important area for understanding atypical eating patterns and for
weight-loss treatment development (19). It is assumed that when
consuming highly palatable or “liked” foods, brain signals activated
are the same as those triggered by drugs of abuse (20, 21). Hedonic
overeating is also linked with obesity, but there are little data on
other adverse correlates (16, 22–25).

4. Animal Models
of Binge Eating,
Purging, and
Hedonic Animal models of binge eating, bulimia nervosa, and hedonic over-
Overeating eating offer a unique opportunity to carefully elucidate these
behaviors that may ultimately benefit human beings. For example,
 1 Introduction 5

animal models allow for isolation of the aberrant eating pattern

from body weight, thereby eliminating the potential confound of
obesity influencing physiology and/or behavior (26). Furthermore,
animal models of bulimia nervosa allow for examination of changes
in neurochemistry (27) that would not be safe or ethical in human
samples. Similarly, hedonic overeating can be modeled in rats to
elucidate brain changes in the reward pathways (28) that would be
too difficult and invasive in human beings.
In conclusion, binge eating, bulimia nervosa, and hedonic
overeating involve unhealthy eating patterns that can have serious
physical and psychological consequences. Animal models are an
innovative research strategy that provide valuable preclinical knowl-
edge and additional information about the biopsychosocial nature
of eating disorders and obesity. In collaboration with human
research, these two approaches have the potential to yield effective
interventions.

Acknowledgements

Research support: NIDDK grant 1R01DK080906 and USUHS

grant R072IC (to M. Tanofsky-Kraff). Disclaimer: The opinions
and assertions expressed herein are those of the authors and are
not to be construed as reflecting the views of USUHS or the U.S.
Department of Defense.

References

1. American Psychiatric Association (2000) syndrome in individuals with binge-eating

Diagnostic and statistical manual of mental dis- disorder. Am J Clin Nutr 91:1568–1573
orders, text revision. American Psychiatric 8. Yanovski SZ, Sebring NG (1994) Recorded
Association, Washington DC food intake of obese women with binge eating
2. Hudson JI et al (2007) The prevalence and disorder before and after weight loss. Int J Eat
correlates of eating disorders in the National Disord 15:135–150
Comorbidity Survey Replication. Biol 9. Goldfein JA et al (1993) Eating behavior in binge
Psychiatry 61:348–358 eating disorder. Int J Eat Disord 14:427–431
3. Swanson SA et al (2011) Prevalence and cor- 10. Raymond NC et al (2007) A comparison of
relates of eating disorders in adolescents. energy intake and food selection during labora-
Results from the national comorbidity survey tory binge eating episodes in obese women
replication adolescent supplement. Arch Gen with and without a binge eating disorder diag-
Psychiatry 68:714–723 nosis. Int J Eat Disord 40:67–71
4. Wonderlich SA et al (2009) The validity and 11. Sysko R et al (2007) Satiety and test meal intake
clinical utility of binge eating disorder. Int J Eat among women with binge eating disorder. Int
Disord 42:687–705 J Eat Disord 40:554–561
5. Marcus MD, Wildes JE (2009) Obesity: is it a 12. Yanovski SZ et al (1992) Food selection and
mental disorder? Int J Eat Disord 42:739–753 intake of obese women with binge-eating dis-
6. Wolfe BE et al (2009) Validity and utility of the order. Am J Clin Nutr 56:975–980
current definition of binge eating. Int J Eat 13. Sherwood NE, Jeffery RW, Wing RR (1999)
Disord 42:674–686 Binge status as a predictor of weight loss treat-
7. Hudson JI et al (2010) Longitudinal study of ment outcome. Int J Obes Relat Metab Disord
the diagnosis of components of the metabolic 23:485–493
6 S.S. Berger and M. Tanofsky-Kraff

14. Masheb RM, Grilo CM, White MA (2010) 22. Stice E et al (2010) Weight gain is associated
An examination of eating patterns in com- with reduced striatal response to palatable food.
munity women with bulimia nervosa and J Neurosci 30:13105–13109
binge eating disorder. Int J Eat Disord 7: 23. Volkow ND, Wang GJ, Baler RD (2011)
618–624 Reward, dopamine and the control of food
15. Fichter MM, Quadflieg N (2004) Twelve-year intake: implications for obesity. Trends Cogn
course and outcome of bulimia nervosa. Psychol Sci 15:37–46
Med 34:1395–1406 24. Volkow ND et al (2008) Overlapping neuronal
16. Lowe MR, Butryn ML (2007) Hedonic hun- circuits in addiction and obesity: evidence of
ger: a new dimension of appetite? Physiol Behav systems pathology. Philos Trans R Soc Lond B
91:432–439 Biol Sci 363:3191–3200
17. Zhang Y et al (2011) Food addiction and neu- 25. Schultes B et al (2010) Hedonic hunger is
roimaging. Curr Pharm Des 17:1149–1157 increased in severely obese patients and is
18. Gold MS et al (2009) Food addiction? J Addict reduced after gastric bypass surgery. Am J Clin
Med 3:42–45 Nutr 92:277–283
19. Avena NM, Gold MS (2011) Food and 26. Corwin RL, Avena NM, Boggiano MM (2011)
addiction—sugars, fats and hedonic overeat- Feeding and reward: perspectives from three
ing. Addiction 106:1214–1215, discussion rat models of binge eating. Physiol Behav 104:
1219–1220 87–97
20. Pecina S, Smith KS (2010) Hedonic and moti- 27. Avena NM et al (2006) Sucrose sham feeding on
vational roles of opioids in food reward: impli- a binge schedule releases accumbens dopamine
cations for overeating disorders. Pharmacol repeatedly and eliminates the acetylcholine sati-
Biochem Behav 97:34–46 ety response. Neuroscience 139:813–820
21. Pelchat ML et al (2004) Images of desire: food- 28. Colantuoni C et al (2001) Excessive sugar intake
craving activation during fMRI. Neuroimage alters binding to dopamine and mu-opioid recep-
23:1486–1493 tors in the brain. Neuroreport 12:3549–3552
 Chapter 2

Binge-Prone Versus Binge-Resistant Rats and Their

Concomitant Behavioral Profiles
Mary M. Boggiano

Abstract
Binge eating is a recalcitrant symptom of bulimia nervosa, binge-eating disorder (BED), and the binge/
purge subtype of anorexia nervosa. Binge eating is rooted in gene–environment interactions, but the biol-
ogy of these interactions is largely unknown. This chapter describes a simple and reliable animal model of
binge eating that is based on such an interaction: a significant inherent difference in eating patterns when
palatable food (PF) is encountered in the environment. Roughly one-third of rats exhibit a binge-like pat-
tern of intake of PF despite normal intake when only chow is available. The PF intake of these binge-eating
prone (BEP) rats is significantly and consistently greater than that of binge-eating-resistant (BER) rats.
Also described are subsequent experimental manipulations that reveal additional parallels between BEP
rats and human binge-eating behavior, including preference for and abnormal intake of PF when stressed,
binge eating in the absence of hunger and despite evidence of satiety, motivation to obtain and eat PF
despite punishing consequences, and age of onset shortly after puberty. The model also dissociates binge
eating from obesity proneness such that four subgroups can be obtained that resemble bulimia nervosa
(binge eating with compensatory restriction to prevent obesity), BED (binge eating with propensity for
obesity), frank obesity (obesity proneness without binge eating), and healthy controls (non-binge-eating,
obese-resistant rats). These behavioral profiles render the BEP/BER model a useful tool to uncover some
of the genetic and epigenetic substrates distinguishing BEDs. It can also be used to develop and test more
targeted treatments against these life-threatening conditions.

Key words: Binge eating, Diet-induced obesity, Eating disorder, Obesity, Rat

1. Introduction

This chapter describes an animal model of binge-eating prone

(BEP) versus binge-eating resistant (BER) rats. Binge eating in
humans is a highly distinct pattern of overeating that is character-
ized by the intake of an abnormally large amount of food in a dis-
crete period of time and is accompanied by a sense of lack of control
over the ability to limit the amount of food eaten or to stop eating (1).

Nicole M. Avena (ed.), Animal Models of Eating Disorders, Neuromethods, vol. 74,
DOI 10.1007/978-1-62703-104-2_2, © Springer Science+Business Media, LLC 2013

7
8 M.M. Boggiano

Binge eating is a stubborn symptom in the binge/purge subtype of

anorexia nervosa, of bulimia nervosa, and of binge-eating disorder
(BED) (1), which collectively afflicts approximately 8% of the U.S.
adult population (2). For brevity, these three disorders will be
referred to here as “binge-eating disorders.”
In its most basic form, the BEP rats most closely model BED
out of all of the eating disorders. This is because caloric restriction
and/or weight loss are not required to produce BEP rats. However,
this chapter describes subsequent manipulations of the model that
can be easily conducted to yield behavioral responses with parallels
to features of bulimia nervosa and binge/purge anorexia. The
BEP/BER model originated from the observation that, while rats
of the same age and sex eat relatively equal amounts of standard lab
chow, their intake will vary when offered highly palatable food (PF).
The PF is high in sugar and/or fat and is given intermittently (e.g.,
2–3 times per week vs. daily) to simulate the “forbidden” regard of
these foods and diagnostic frequency in clinical binge eating (1, 3, 4).
The key observation is that approximately one-third of the rats
consistently eat the highest, and one-third eat the lowest, amount of
the PF (5). This stable pattern is consistent with the established
chronic and stable nature of binge eating in BED (6). Importantly,
the expression of binge eating in the BEP rats is not observed until
they come in contact with PF. That is, BEPs and BERs are indistin-
guishable until exposed to an environment containing PF. BEPs
also do not have to learn to overeat PF; they inherently overeat dur-
ing the first exposure. This is important because it represents an
example of a gene–environment interaction. Gene–environment
interactions are pathogenic of eating disorders, yet are not researched
as aggressively as they need to be (7, 8).
Our work suggests that the only environmental factor needed
to elicit the BEP/BER model is PF. The salience of PF in human
binge-eating behavior cannot be understated. Since these foods are
typically high in refined sugars and fat, they are rewarding and
calorie dense, and are therefore regarded as “forbidden foods”
outside of binges. They are obsessed over, craved, and overcon-
sumed during binges (4, 9, 10). Intake of just a morsel of PF or
simply the smell of PF is known to trigger relapses back to binge
eating (11–13). It is not possible to estimate the extent to which
exposure to PF is necessary for the development of BEDs because
of its ubiquitous nature in the modern world. We are exposed to
these foods from childhood and even as neonates (14, 15).
Nonetheless, the reliance of the BEP/BER model on PF exposure
does not devalue the model as a research tool in BEDs, especially
considering the salient role of PF in these disorders.
The numerous parallels between BEP rat behavior and clinical
binge eating validate its use as a preclinical tool. These parallels go
beyond binge eating in a discrete period of time and the stable
nature of the binge-eating pattern. Here we describe additional
parallels that emerge when the rats are subjected to factors relevant
 2 Binge-Prone Versus Binge-Resistant Rats 9

to life experiences of those with BEDs. These factors include stress,

hunger, tolerance of painful consequences in order to binge on PF
even when sated, and exposure during puberty. In all cases, BEP
rats respond with striking similarity to individuals with BEDs
(5, 16, 17). The BEP/BER model also recapitulates the indepen-
dence between binge eating and propensity to develop obesity.
Given the large weight range of patients with BEDs, it is not sur-
prising that familial studies confirm a strong genetic contribution
for binge eating that is independent of the obesity phenotype
(18, 19). Here too is described how it is possible to obtain four
subgroups from the BEP/BER model that are behaviorally similar
to bulimia nervosa, BED, non-BED obesity, and healthy controls
(5). These subgroups could prove useful in the discovery of genes
that distinguish propensity for each of these conditions. In so
doing, more targeted treatments can be designed. Lastly, the model
promises to help identify the exact physiological changes that take
place when modern “super-hedonic” food ingredients and predis-
posing genes intersect. This type of research is needed to learn how
to best prevent or decrease the recidivistic nature of BEDs.

2. Materials
and Procedures
2.1. Animals Young adult female Sprague–Dawley rats (Harlan, IN and WI) are
used in keeping with the higher female incidence and age of onset
of BEDs (2, 7). The rats may be older in age but not pre-pubertal
(17). The typical results presented here are those obtained with
60-day-old rats. Regarding the number of rats required at the
onset, the BEP/BER model relies on extreme amounts of PF con-
sumed. These extremes are best observed from an initial group
that is three times the number of rats desired in the BEP and BER
group. For example, for N = 10 BEPs and N = 10 BEPs (a typical N
per group in the author’s and others’ rodent studies), one would
start with N = (10 × 3) or 30 rats. Of course, the number of BEP
and BER rats required will depend on the complexity of the study
design; e.g., drug versus control conditions may require 20 rats per
group if working with a between-groups design in which case a
good start number would be (20 × 3) or 60 rats. Multiple studies
confirm the reliability of the “N × 3” formula because roughly one-
third of female rats will meet BEP and one-third will meet BER
criteria (5, 16, 17, 20, 21). The rats can be single or pair-housed
when not being tested and should be acclimated to standard col-
ony conditions with a 12:12-h dark/light phase. Lights should be
timed to turn off at the onset of the feeding tests; e.g., if feeding
tests wish to be conducted at 1000 hours then lights should go off
at 10 a.m. (1000 hours). This captures intake during the initial
dark period. Rats should be well acclimated to any new light/dark
schedule as for any other study.
10 M.M. Boggiano

2.2. Diet The rats are maintained on ad libitum water and standard rat chow
(e.g., Harlan Teklad Global Diets, IN; 3.3 kcal/g) throughout the
studies. To identify BEP and BER groups, a PF must be intro-
duced. Most studies have used Oreo Double-Stuf ® cookies
(4.8 kcal/g; Nabisco, NJ) (5, 16, 20). Oreos® have worked well in
other models of binge eating (5, 20, 22–24) and include the high-
fat and sugar contents that are typically craved and overeaten by
humans who are binge eating (3, 4). Other PFs have been used
successfully (5, 17, 21), but the results given here are those resulting
with the use of Oreos®. The use of other PF types is discussed in
Sect. 3. The PF is always given alongside standard rat chow.

2.3. Identifying BEP BEP and BER rats are identified by a series of “feeding tests.” All
and BER Rats rats are first allowed to overcome neophobia by introducing a few
grams of the PF (e.g., half a cookie) in home cages prior to the
feeding tests. The rats are then subjected to four measured feeding
tests. Each test consists of placing a generous premeasured amount
of the PF (e.g., two Oreo® cookies, ~29 g) and chow pellets (e.g.,
10 g) inside of or on the lid of the home cages just prior to lights
out. Intake is measured after 4 h under red or dim lighting. The
cookies remain in the cage for 24 h. Care should be taken to include
any spillage, although it tends to be minimal with these types of
foods. The 4-h interval is a discrete period of time that provides
measurable differences in intake between groups in this and other
models of binge eating (20, 22–25). Food intake can be measured
at any other intervals up to 24 h, but is not necessary for the
identification of BEP/BER status. Body weights can be recorded
periodically to confirm no change in weight between the groups
over time. However, body weights are also not necessary in deter-
mining BEP/BER status. Importantly, the feeding tests are sepa-
rated by at least 1 day of only ad libitum chow. Typically the PF
and chow feeding tests occur 2–3 times per week. This renders PF
intake as an intermittent event, simulating the two times per week
criteria for binge eating (1) and the “forbidden food” regard for
PF in BEDs (4, 9, 10). Periodic 24-h measures of chow intake on
the chow-only days serve to confirm that there is no significant dif-
ference in amount of this food eaten between BEP and BER rats.
Differences are only observed with PF. Once BEP/BER status is
established using the criteria described in Sect. 2.4, the feeding
tests can occur less frequently (e.g., one time per week) for subse-
quent experimental manipulations.

2.4. Criteria Used For each of the four feeding tests, the kcal intake of PF of each of
to Classify BEP the rats is grouped into tertiles. That is, the values and their cor-
from BER Rats responding rat identification are evenly distributed into three
groups: a lowest, a middle, and a highest PF-intake group. Rats in
the lowest PF-intake tertile across all four of the feeding tests, or in
three out of the four tests, are assigned BER status. Those in the
highest PF-intake tertile across all four, or three out of the four
 2 Binge-Prone Versus Binge-Resistant Rats 11

tests, are assigned BEP status. How consistently a rat appears in a

particular tertile is more important in determining status than the
absolute kcal value of PF consumed—extreme as it might be if the
rat appears in more than one tertile. Rats falling into the middle
tertile do not need to be retained for further BEP versus BER tests
unless one wishes to maintain the rats on chow throughout as a
chow-control group. This is an appropriate control because all rats,
regardless of BEP or BER or “middle” status eat equivalent
amounts of chow when only chow is available.
Alternatively, the middle group can be treated as a third “mid-
dle PF-eating” group, but the caveat must be considered that some
of the rats making up this group were placed in the group because
of their inconsistent amount of PF intake. Another option, and
one used by the author, is to retain the middle rats to pilot test any
experimental variables before they are tested on the BEP and BER
rats. This is useful given that the rats are of the same age, sex, and
body weight as the BEP and BER rats. But again, if time, labor,
and cost are an issue, and if the study aims permit, the middle ter-
tile rats need not be used at all. At the end of the feeding tests,
there should be an equal number of BEP and BER rats. Subsequent
PF + chow feeding tests can be conducted to confirm the stability
of the BEP/BER patterns, but these should be preceded by at least
1 day of only chow with no experimental manipulations. The typi-
cal BEP/BER intakes one can expect are described in the Sect. 3.

2.5. Time Required If the feeding tests are administered 2–3 times per week, BEP and
BER rats can be identified within two weeks’ time.

2.6. Data Analysis Frequency descriptive statistics set at 33.3% percentiles will yield
tertile groups of PF intake for each feeding test. Cronbach’s alpha
can be used to verify consistency of high versus low PF intake
within rats across the feeding tests. Student’s t-test or ANOVA is
used to compare differences between BEPs and BERs on PF intake,
chow intake, and body weights. Bonferroni or Tukey post hoc tests
are used if more than two groups are compared, e.g., if the middle
group is analyzed. The alpha level for all comparisons is 0.05. More
complex designs have been used, such as mixed within-subject and
repeated measures ANOVAs (20), and mixed linear models when
measuring changes over time (17). All food intake data should be
converted to and analyzed as kilocalories, especially when combin-
ing measurements of intake of various energy-dense foods.

3. Notes and
Anticipated
Results
The following variables are not necessary to obtain the BEP/BER
model, but they yield additional behavioral profiles in BEP rats
that parallel features of binge eating. These can serve as additional
12 M.M. Boggiano

“models” according to the characteristics one wishes to explore

further. Given the simplicity of obtaining BEP and BER groups,
these subsequent manipulations do not require much additional time
to perform. All of the variables described below were tested in a
between-groups design starting with N = 60 rats for N = 20 BEP and
N = 20 BER young adult female Sprague–Dawley rats, except where
noted. If rat labor and upkeep, but not time, are issues, half the rats
per group (e.g., N = 8–10/group) is acceptable for most within-
subjects designs. The results of these manipulations and their relevance
to understanding binge-eating behavior in humans are described
below, as are alternate methods of conducting these tests.

3.1. Effect of Acute Once rats are classified as BEP or BER and following at least 2 days
Food Deprivation on of chow-only feeding, half of the rats from each group are given
BEP Versus BER Rats 50% of their normal 24-h chow intake at lights out. The reduced
amount is 50% of the mean of all the rats’ previous day’s 24-h
chow intake. The other half of the rats of each group remain on ad
libitum chow. On the following day just prior to lights out, all rats
are given a premeasured amount of PF and chow, as in the feeding
tests, and intakes are recorded after 1, 4, and 24 h. More frequent
recordings can be taken if needed.

3.2. Effect of Stress on Stress typically has anorectic effects on laboratory rats (26, 27).
BEP Versus BER Rats The exception is when stress is combined with a “history of dieting,”
which the author used to develop a different model of binge eating
(22, 24) (also see Chap. 3 for innovative variations on this model).
The BEP/BER model does not require caloric restriction or diet-
ing simulations, so the rats are not expected to overeat when
stressed. Nonetheless, stress evokes interesting and clinically rele-
vant differences between the BEP and BER rats. Once the rats are
classified as BEP or BER and following at least 2 days of chow-only
feeding, half of the BERs and half of the BEPs are individually
subjected to four 3 s bouts of 0.6 mA of scrambled foot shock in a
shock alley apparatus, prior to lights out. The other half of the rats
in each group is placed in the shock alley for the same amount of
time without shock.1 The rats are then returned to their home
cages while lights are still on, with a premeasured amount of PF
and chow as in the feeding tests. Intakes are recorded after 2 and
4 h of feeding.

3.3. Effect of Suffering This test of motivation for PF uses the same foot shock apparatus
Consequences for PF as in the stress procedures above. Here N = 10 BEP and N = 10
in BEP Versus BER BER rats naïve to foot shock are allowed to eat ad libitum amounts
Rats of chow in their home cages during the first 2–4 h in the dark. This
precludes hunger from confounding this test, which is intended to

1
Additional details on this manipulation are in (5); shock apparatus details can
be found in (22).
 2 Binge-Prone Versus Binge-Resistant Rats 13

measure motivation for the rewarding versus metabolic properties

of PF intake. The rats are then allowed to individually roam in the
shock alley under red light to acclimate to the space and to learn
that one end of the alley is baited with PF. Plain M&M’s® candy
(Mars, McLean, VA) has been used, but it is likely that another PF
such as Froot Loops (Kellogg, MI) or small flavored pellets
(Research Diets, NJ) would work as effectively (28). Acclimation
to the alley is confirmed when all rats take at least one bite of an
M&M® during the first minute after being placed into the shock-
free end of the alley. This typically occurs after three 10-min ses-
sions in the alley (over 3 days). On the first day of actual testing, the
rats are placed in the alley for 10 min, but with no shock, in order
to obtain a baseline measure of PF intake under these conditions.
On the second day, the lowest level of shock (0.10 mA) is adminis-
tered for 3s immediately following retrieval of an M&M®. The
candy must be completely removed from the food hopper by paw
or mouth before shock is delivered. This level of shock is readmin-
istered for as many times as the rat returns and retrieves an M&M®
during a single 10-min session. In each 10-min session thereafter
(on the following days), the shock level is increased by 0.05-mA
increments until the rat no longer retrieves PF. On the test day fol-
lowing a session where the rat chooses not to retrieve an M&M®,
the rat is given a last chance to retrieve and if there is no attempt
within the 10-min session, the rat is no longer put into the alley for
the duration of the study. When placed into the alley, the rats are
always placed in the end of the alley that is not baited with food or
wired to shock.2 Measures recorded include number of M&M’s®
retrieved, amount of M&M’s® kilocalories consumed per session at
each shock level, and the highest shock level tolerated per rat.

3.4. Effect of a Clinical binge eating occurs in individuals that maintain a wide
High-Fat Diet on the range of body weights, e.g., binge eating occurs in underweight
Propensity of BEP anorexia nervosa, normal weight bulimia nervosa, and overweight
Versus BER Rats to or obese BED patients (1). Hence, the susceptibility to develop
Develop Obesity obesity should be independent of binge-eating status. To test for
this, N = 20 BEP and N = 20 BER, which never significantly differ
in body weight, are subjected to a traditional diet-induced obesity
(DIO) protocol (29, 30). Under the DIO protocol, all the rats are
provided with a daily sole ad libitum diet of 35% fat pellets
(Research Diets, Diet # D12266B, New Brunswick, NJ) in their
home cages for a minimum of 14 days. Body weights and 24-h
food intakes are recorded daily or at minimum on days 1 and 14.
During statistical analyses, body weights on day 14 of half of the rats
that gain the most weight are compared to weights of the other half
of the rats that gain the least weight, regardless of BEP/BER status.

2
Refer to (16) for additional details.
14 M.M. Boggiano

Fig. 1. Typical 4-h intake patterns of binge-eating resistant (BER) versus binge-eating prone (BEP) rats; N = 20/group.
(a) When only chow is available the groups are indistinguishable by their intake (ns). (b) When PF is available with chow,
BEPs consistently consume >40% more PF kilocalories than BERs (***p < 0.001). The effect is also observed with a smaller
N = 8–10 rats/group (16, 17, 20, 21). Reproduced, with permission, from (5).

A statistically significant difference in the means will confirm the

success of the DIO protocol to identify obese-prone from obese-
resistant rats. Then a chi-squared test can be used to determine if
there are a different number of BEP versus BER rats in the obese-
prone versus obese-resistant groups. Equal numbers of BEPs and
BERs are expected in each weight group given the independence
of binge eating from obesity proneness.

3.5. Effect One may wish to use this model to examine environmental or physi-
of Developmental ological correlates of early-life experience, puberty, or aging on binge
Factors on the eating. Klump and colleagues investigated the age of onset and effect
Expression of BEP of estradiol removal on BEP/BER patterns in female Sprague–
Versus BER Patterns Dawley rats. The PF for the feeding tests was 15–20 g of Betty
Crocker Vanilla Frosting (General Mills, MN) in a dish suspended
inside the cage. More was added as needed with the rats’ growth
over time. The feeding tests were conducted as described above and
occurred three times per week from postnatal day P23 through P69.
Puberty onset occurred at P34-P39 (defined as vaginal opening),
during which time feeding tests were conducted only one time per
week. In sum there were six feeding tests in pre-early puberty, four
in mid-late puberty, and five in adulthood. Mixed linear models
analyses were used to compare PF intake, chow intake, and body
weight during age development in BEP versus BER rats (17). In a
separate study, adult BEP and BER rats were ovariectomized (OVX)
at age P70 or P71 and subjected to four additional feeding tests on
day P79 through P86. A second study controlled for any effects due
to the surgery by including sham-operated rats (21).

3.6. Typical/ The feeding tests yield two groups of rats that never differ in the
Anticipated Results amount of plain chow intake if they only have access to chow
(Fig. 1), but that differ consistently (Cronbach’s alpha = 0.86) and
significantly in the amount of PF they consume. As shown in Fig. 1,
 2 Binge-Prone Versus Binge-Resistant Rats 15

the BEP group typically consumes >40% more PF kilocalories by

4 h (55% shown here) than do the BERs. The statistical difference
in PF intake can actually be observed as early as the first hour of
eating (5) (not shown) but the 4-h period assures that rats have
eaten to satiety and it is also a time interval when BEP/BER dif-
ferences are the largest. By 24 h, the BERs approach but do not
quite match the BEPs’ PF intake (5). Replications of the model
have obtained similar BEP/BER differences with as few as N = 8–10
rats per group (16, 17, 20, 21). Tests using the middle PF eaters
show that they eat an amount of PF intermediate with that of the
BER and BEP groups (5). There is never a significant difference in
body weights between the two groups due to the intermittent
access to PF. In line with the stable nature of clinical binge eating
(6), the BEP/BER patterns are stable. Consistent patterns have
been observed even after multiple manipulations, some noxious,
including acute and cyclic food deprivation, foot shock, contextual-
cue conditioning, exposure to other PFs (5, 16, 20), and surgeries
(21). Eating a larger amount of food than normally expected,
within a discrete period of time, and with a sense of lack of control
to limit intake are diagnostic features of binge eating (1). Likewise,
BEPs consume an amount of food clearly larger than normal, in a
discrete period of time. This is not only due to the fact that their
intake is being compared to the extreme lowest PF-eating rats
because they can also eat a significantly greater amount of PF than
the middle PF eaters (21). They also seem unable to regulate the
amount of PF they consume despite the fact that, when only chow
is available, they consume as much as BERs, which hints of normal
satiety function. Hence, exceeding this level of food intake sug-
gests that they ignore satiety signals when bingeing on PF. The
results from the hunger test below support this assumption.

3.6.1. Effect of Acute Food As shown in Fig. 2, a period of caloric restriction causes BERs to eat
Deprivation on BEP Versus significantly more food then when sated. This increase consists of
BER Rats greater chow intake, which is typical of rats hungry from metabolic
deficit (25, 31). BEPs, too, eat proportionally more chow than
when sated and so appear to respond normally to hunger. Also,
because hungry BEPs do not eat more total kilocalories than hun-
gry BERs, it can be implied that they also have normal satiety.
However, as also shown in Fig. 2, the amount of total kilocalories
that BEPs eat under restricted conditions matches the amount of
calories they take in under sated conditions. This behavior is clearly
abnormal especially given the behavioral indices of normal hunger
and satiety cues in these rats. The responses just described are
observed in the 4th hour of feeding but can all be observed as early
as after the 1st hour of feeding (5). Clinical binge eating also appears
to be unaffected by hunger and satiety cues. Indeed, hunger is one
of the weakest triggers of binge eating and binges are diagnostically
defined as occurring in the absence of hunger (1, 32–34). In
humans, a more potent trigger is stress (34–38).
16 M.M. Boggiano

Fig. 2. Amount of chow and PF consumed by BEPs and BERs (N = 10/per condition) under
calorically restricted or hungry versus ad libitum or sated conditions. BERs eat more total
kilocalories after a period of deprivation,*p < 0.05, and both groups eat proportionately
more chow kilocalories under food deprived than sated conditions, ***p < 0.001. However,
BEPs eat as many kilocalories when sated as when they are hungry after a period of food
deprivation (ns). Reproduced, with permission, from (5).

3.6.2. Effect of Stress on As seen in Fig. 3, at 2 h following foot shock, stressed BERs
BEP Versus BER Rats consume less food than when not stressed. This is the expected and
normal response of rats to laboratory stressors (26, 27). However,
stressed BEPs fail to display this normal hypophagia and in fact
appear to be completely unaffected by shock. By 4 h, stress causes
BERs to remain hypophagic. Notably, they are eating less PF, not
less chow. By this time BEPs appear somewhat affected by the
stress, but their decrease in intake is due to forsaking the healthy
chow over PF. Their PF intake remains abnormally elevated. By
24 h, the intake of each group normalizes to match their counter-
parts’ intake under nonstressed conditions. The behavior of BEPs
under stress resembles that of human binge eating in that stress
triggers overeating versus undereating and is associated with
increased consumption of PFs (34–37). In human binge eating,
stress may actually make PFs more rewarding (38). Just how
rewarding BEP rats find PF can be seen by how much punishment
they are willing to tolerate for it.

3.6.3. Effect of Suffering As shown in Fig. 4, BEPs make significantly more M&M® retriev-
Consequences for PF in als than BERs. This difference reaches significance at shock levels
BEP Versus BER Rats of 0.25 mA and higher. At 0.40 mA and higher, only one BER
versus 8 BEP rats braved shock for M&M’s®. Only BEP rats con-
tinue to cross at 0.60 mAs (Fig. 4). As also seen in Fig. 4, the
retrieved M&M’s® are consumed as evidenced by the 2-fold greater
kcal intake of M&M’s® by BEPs versus BERs across all shock levels
(16). In sum, the BEP rats’ willingness to tolerate increasing pain
and anxiety associated with foot shock models the addictive-like
 2 Binge-Prone Versus Binge-Resistant Rats 17

Fig. 3. Amount of chow and PF consumed by BEPs and BERs following foot shock stress
or no stress (N = 10/condition). (a) In the first 2 h, only BERs show a normal anorectic
effect to stress, **p < 0.01 versus unstressed BERs. At this time, BEPs are not affected by
stress. (b) By 4 h, there is evidence of a stress-induced anorectic effect in BEPs but the
decreased intake is on chow, not PF intake (#p < 0.05). Conversely, at 4 h, BERs forsake
PF, not chow, when stressed (*p < 0.05). Reproduced, with permission, from (5).

nature of human binge-eating where motivation to binge-eat per-

sists despite the mounting psychological and physical consequences
directly associated with this behavior (1, 39–41).

3.6.4. Effect of a High-fat When BEP and BER rats are fed a high-fat diet for 2 weeks, exactly
Diet on the Propensity of half of the BERs and half of the BEPs develop obesity while the
BEP Versus BER Rats to other half of each BEP and BER group resist weight gain. The
Develop Obesity obese-prone rats gain approximately 8.3% of initial body weight vs.
a 1.9% gain by the obese-resistant rats (p < 0.01) (5). This is due to
the obese-prone rats’ failure to decrease their normal volume of
food when forced to eat the more calorie-dense high-fat diet.
Importantly, BEPs are as likely to do this as BERs. Each group is
also as likely to voluntarily restrict the amount of the high-fat diet
which results in maintaining normal weight.
18 M.M. Boggiano

Fig. 4. (a) More BEP versus BER rats are willing to cross incrementing levels of foot shock to obtain M&M® candies;
**p < 0.01; N = 10/group. (b) The retrievals are also consumed by the BEPs for a final greater intake of M&M’s® vs. BERs
across all levels and statistically significant at some of the levels denoted by *p < 0.05; and **p < 0.01. Reproduced, with
permission, from (16).

At the end, the DIO protocol yields four subgroups that can
be used to investigate possible biological differences between buli-
mia nervosa, BED, non-binge-eating obesity, and healthy controls
(see Table 1). For example, some individuals with bulimia or BED
resist obesity through compensatory behaviors, including limiting
caloric intake (1, 42). Similarly, the obese-resistant BEP rats reduce
their volume of high-fat intake, thereby reducing total kilocalories
consumed to maintain normal body weight. Not all human moti-
vations to restrict caloric intake can be modeled in rats, but there
may be a common physiology between bulimia nervosa patients
and BEP-obese-resistant rats that enables them to reduce caloric
intake amidst PF, a physiology possibly compromised in BEP-
obese-prone rats and obese individuals with BED.
 2 Binge-Prone Versus Binge-Resistant Rats 19

Table 1
Clinical conditions represented by the four subgroups that result from placing
BEP and BER rats on a traditional diet-induced obesity (DIO) protocol

BER BEP

Obese-Resistant Healthy Bulimia Nervosa

These rats do not have a binge pattern These rats have a binge pattern on
on intermittent PF and when placed intermittent PF but remain lean when
on a forced high-fat diet stay lean by placed on a forced high-fat diet by
voluntarily eating less voluntarily eating less or by “com-
pensating” for the increased calories
Obese-Prone Frank obesity Binge-eating disorder
These rats do not have a binge pattern These rats have a binge pattern on
on intermittent PF but gain weight intermittent PF and gain weight on a
on a forced high- fat diet because forced high-fat diet because they fail
they fail to adjust their intake for to compensate for the additional
the additional calories of that diet calories of that diet
BER binge eating resistant, BEP binge eating prone rats based on difference in intake of palatable food (PF) during
feeding tests used to identify the groups (see text for procedures). Obese-Resistant and Obese-Prone groups (p < 0.01
difference in weight gain) emerge from switching BEP and BER rats to a no-choice high-fat diet. Exactly ½ of BEP and
½ of BER rats develop obesity while the other ½ of BEP and BER rats resist weight gain. N = 10 per subgroup (5)

3.6.5. Effect As is typical of the BEP/BER model in the author’s hands, Klump
of Developmental Factors and colleagues found that roughly one-third of an initial group of
on the Expression of BEP thirty rats could be clearly classified as BEPs and one-third as BERs
Versus BER Patterns based on their significant difference in amount of PF intake (17).
Of major importance is that when they observed PF intake patterns
across time, they found that the onset of the BEP phenotype does
not appear until mid-late puberty (P39-P58). This seminal change
in PF intake occurred as chow intake during chow-only days, and
body weights, remained the same for both groups. Only PF intake
differed. The emergence of PF binge eating shortly after puberty
was replicated in a separate squad of N = 36 rats that were exposed
to more frequent feeding tests during puberty (three times per
week vs. one time per week) (17). The results are a compelling
parallel to the age of onset for eating disorders, which is after
puberty (1, 2, 43). Results from the OVX study revealed that OVX
caused an expected increase in general food intake and body weight
across all hormone-depleted rats, regardless of BEP or BER status.
However, the OVXed BEP rats still continued to eat significantly
more PF than the OVXed BER rats (21). The fact that BEP/BER
patterns remained stable despite removal of estradiol indicates that
other—yet unknown—signals activated at puberty are needed to
express binge eating. While these results were at first surprising
given that the BEP pattern appears after and not before puberty,
they are consistent with the fact that a significant number of men,
and not only women, develop BEDs (2).
20 M.M. Boggiano

Fig. 5. The BEP/BER patterns generalize to other PFs including those containing mainly sugar (Froot Loops)®, mainly fat
(Crisco)®, or combinations of both (cookies, pellets). All are preferred by both groups (N = 20/group) over chow but, with the
exception of candy corn, BEPs eat significantly more of them than do BERs; *p < 0.05, **p < 0.01, ***p < 0.001. Reproduced,
with permission, from (5).

3.7. Troubleshooting In the rare event that not enough rats meet the four-out-of-four or
and Guidelines if three-out-of-four feeding test criteria for consistency in PF intake,
Altering Variables additional tests should be conducted. When choosing BEP rats, if,
after selecting the most consistent eating animals, the choice must
3.7.1. Identifying BEP/BER
be made between selecting a rat that ate in the highest quartile
Status
three times and once in the lowest quartile versus a rat that ate
three times in the highest quartile and once in the middle quartile,
the latter should be chosen into the BEP group because the middle
values are closer to the high end of intake. The same applies to
selection of BER rats (middle intake is closer to the lowest tertile
than the highest tertile). There is no specific amount of kilocalories
that determine BEP or BER status. As pointed out by Klump et al.,
this also parallels the method by which clinical binge-eating was
first defined; it was based on comparing women in the high vs. low
ends of the binge eating distribution (1, 17).

3.7.2. Using Other Most studies have used either Oreo cookies (5, 16, 20) or Betty
Palatable Foods to Identify Crocker® Vanilla Frosting (General Mills, MN) (17, 21). Figure 5
BEP/BER Status illustrates that rats first identified as BEP/BER with Oreos®, exhibit
the same patterns of intake on other PFs, including high-fat pellets
(Research Diets, Diet # D12266B, NJ), Oreo-flavored pellets
(Research Diets, NJ), Froot Loops® (Kellogg, MI), Crisco®
(Proctor & Gamble, OH) (5), and M&M’s® (16). Hence, it may
be possible to identify BEP and BER rats with nonfat sugary (e.g.,
Froot Loops) or nonsugar fatty PFs (e.g., Crisco®) and not just
mixed macronutrient PFs like Oreos® and frosting. Still, one is
warned to first test any new PF. For example, Fig. 5 illustrates that
one of the PFs tested, Candy Corn (Brach’s Confections, TN),
failed to yield a significant difference between groups although it
 2 Binge-Prone Versus Binge-Resistant Rats 21

was still preferred over chow by both groups (5). Hence not all PFs
may dissociate BEPs from BERs. It may be that some PFs produce
negative alliesthesia more quickly than others and BEPs may be as
sensitive to this as BERs. Salty snack foods have not been tested,
but are predicted to discern BEP/BER groups given that rats find
them rewarding (44).

3.7.3. Using Alternate If foot shock is not practical, there is no reason that other standard
Modes of Stress-Induction laboratory stressors, including immobilization, cold temperature
or water exposure, social defeat, noise, or emotional stress, should
not yield the same differences in responses to stress observed in the
BEP and BER rats. A particular “human-like” stressor, to the
extent that craving can be regarded as stressful, is to dangle the PF
in front of the rats without allowing them access to it. This has
been used successfully in replications of the author’s stress + dieting
model of binge eating, which originally used foot shock (45).

3.7.4. Intermittent Versus The intermittency of PF used in this model is integral. If instead,
Chronic Access to PF rats are allowed daily access to PF and chow, the model is compro-
mised because over time (within 2 weeks) the PF intake of BEPs
and BERs become comparable. This is due to an eventual decrease
in PF intake among the BEPs (5). The model relies on the inter-
mittent, not daily, access to PF, which closely models how indi-
viduals with BEDs eat (1). PF is regarded as “forbidden” (4, 9, 10)
and there is evidence that sporadic access to PF may exacerbate
binge eating by increasing its rewarding quality (46).

3.7.5. Using Male Versus Currently there are no published studies using male rats with this
Female Rats model. However, Klump et al. report that age-matched males do
not ingest as much PF (vanilla frosting) as females, and hence do
not exhibit the wide range of PF intake needed to be classified as
BEPs or BERs (personal communication, October 9, 2011). While
male rats still prefer the PF to chow, they eat proportionately more
chow during meals than do young females, likely because of
increased protein needs. The lower incidence of male rats to achieve
BEP status may offer future explanations for the lower male-to-
female ratio in BEDs. However, the effects in the male rats may be
confounded by the type of PF used. Gender is known to influence
PF preferences. Male rats and humans prefer palatable fat/protein
or “savory” combinations, and female rats and humans prefer car-
bohydrate or “sweet” combinations (47–49). Therefore, attempts
to replicate this model with male rats should first test the PF to be
used; it should yield a range of consistent intakes wherein the high-
est and lowest amounts consumed are statistically different.

3.7.6. Conducting Drug studies have not yet been conducted with this model. Since
Pharmacological Tests the BEP/BER patterns remain stable and robust even after surgical
procedures and aversive manipulations like foot shock, it is not
22 M.M. Boggiano

expected that drug administration procedures will compromise the

model so long as the rats are first acclimated to the procedures.
Acclimation to injection procedures should be assured and followed
with another “feeding test” to confirm the BEP/BER patterns
prior to any drug testing.

3.7.7. Using Other Rat Only Sprague–Dawley rats have been used so far with this model,
Strains or Species but it is expected that results replicate in other inbred or selectively
bred strains of rats. Mice have not been used, but since they show
clear preferences for PF, including food used in the BEP/BER
model here with rats (50), it may be possible to use mice if their
patterns of PF intake are determined to be stable.

4. Conclusion

The BEP/BER model offers a simple, quick, and reliable method

by which to study human binge eating. Pavlov posited that a simple
reflex could give clues as to the mechanisms behind some of the
most complex reactions between humans and their environment
(51). Eating disorders are certainly complex reactions to the envi-
ronment. The BEP/BER model was developed by targeting one
simple “reflex-like” symptom: that of overeating once PF enters
the mouth. Once rats with an inherent penchant to do this (BEPs)
are identified and discerned from those without (BERs), it is dis-
covered that there are many more behavioral parallels to human
binge eating than eating abnormally larger amounts of food in a
discrete period of time. Like clinical binge eating, BEPs binge in
the absence of hunger, the binges override satiety, PF intake remains
high under stress, BEPs tolerate aversive consequences for PF, and
only some are prone to obesity. Also as is typical of human BEDs,
the age of onset for the BEP binge pattern is shortly after puberty.
The BEP/BER model also offers a tool with which to investigate
a variable that warrants much more attention in eating disorders
research, namely the biological changes that take place to explain
how factors in the environment interact with predisposing genes to
express eating disorder symptoms (7, 8). PF is ubiquitous in the
environment, as are stress and dieting, yet not all develop eating
disorders when subjected to these. The BEPs never learn to over-
eat PF, but instead do this upon first encountering PF. Therefore,
binge eating is a preexisting disposition that is expressed when
exposed to PF. The identification of genetic and epigenetic mark-
ers that confer the BEP versus BER phenotypes once PF is eaten
(and once puberty sets in) should help clarify the physiology of
binge eating. Similarly, identification of gene markers in the four
subgroups obtained from subjecting BEPs and BER to a high-fat
diet should shed light on the physiology that predisposes some
 2 Binge-Prone Versus Binge-Resistant Rats 23

who binge eat to develop BED vs. bulimia nervosa, and to develop
obesity with and without binge eating.
Lastly, the BEP/BER model attests to the incredible value of
animal models in eating disorder research. BEP rats display behav-
iors such as willingness to cross painful shock for M&M’s®, inabil-
ity to limit PF intake despite normal hunger–satiety cues, and in
some, an ability to restrict calories and prevent weight gain despite
the stable trait to binge eat. They also do not start bingeing until
they reach puberty. These are responses that in humans with BEDs
are commonly attributed to processes only capable in humans (e.g.,
cognitive dysregulation, irrational thinking, concern with body
weight and shape, judgment by peers and the opposite sex). Clearly,
researchers cannot mimic all motivations that drive human binge
eating in rats, but it is clear that there is a more basic “reflexive”
biology underlying binge eating when many of these complex
behaviors are observed in rodents. This biology can be exploited
with the help of the BEP/BER model, as well as with other animal
models in this book, to prevent the expression of eating disorders
altogether, or, at minimum, to develop superior treatments for the
millions that suffer from them.

Acknowledgments

This research was supported by the NIH DK-066007 grant and

UAB Support for Development and Application of Research Using
Animal Models award to MMB. Special thanks are extended to
Dr. Kelly Klump and colleagues for their steady communication of
compelling findings with this model. Also thanks to Dr. Paul
Blanton for his assistance in manuscript editing.

References
1. American Psychiatric Association (2000) obesity with and without binge-eating. Int J
Diagnostic and statistical manual of mental dis- Obes 31:1357–1367
orders, Revised 4th Ed. American Psychiatric 6. Pope HGJ et al (2006) Binge eating disorder: a
Association, Washington, DC stable syndrome. Am J Psychiatry 163:
2. Hudson JI et al (2007) The prevalence and 2181–2183
correlates of eating disorders in the National 7. Striegel-Moore RH, Bulik CM (2007) Risk
Comorbidity Survey Replication. Biol factors for eating disorders. Am Psychol
Psychiatry 61:348–358 62:181–198
3. Davis C et al (2008) Personality and eating 8. Campbell IC et al (2011) Eating disorders,
behaviors: a case–control study of binge eating gene-environment interactions and epigenet-
disorder. Int J Eat Disord 41:243–250 ics. Neurosci Biobehav Rev 35:784–793
4. Kales EF (1990) Macronutrient analysis of binge 9. White MA, Grilo CM (2005) Psychometric
eating in bulimia. Physiol Behav 48:837–840 properties of the Food Craving Inventory
5. Boggiano MM et al (2007) High intake of pal- among obese patients with binge eating disor-
atable food predicts binge-eating characteristics der. Eat Behav 6:239–245
independent of susceptibility to obesity: an ani- 10. Fullerton DT et al (1985) Sugar, opioids, and
mal model of lean vs. obese binge eating and binge eating. Brain Res Bull 14:673–680
24 M.M. Boggiano

11. Rogers PJ, Hill AJ (1989) Breakdown of 28. Hagan MM, Moss DE (1995) Effect of peptide
dietary restraint following mere exposure to YY (PYY) on food-associated conflict. Physiol
food stimuli: interrelationships between Behav 58:731–735
restraint, hunger, salivation, and food intake. 29. Chandler PC et al (2005) Feeding response to
Addict Behav 14:387–397 melanocortin agonist predicts preference for
12. Waters A, Hill A, Waller G (2001) Internal and and obesity from a high-fat diet. Physiol Behav
external antecedents of binge eating episodes in 85:221–230
a group of women with bulimia nervosa. Int J 30. Levin BE, Dunn-Meynel AA (2002) Defense
Eat Disord 29:17–22 of body weight depends on dietary composi-
13. Jansen A, van den Hout M (1991) On being tion and palatability in rats with diet-induced
led into temptation: “counterregulation” of obesity. Am J Physiol 282:R46–54
dieters after smelling a “preload”. Addict Behav 31. Glass MJ, Billington CJ, Levine AS (2000)
16:247–253 Naltrexone administered to central nucleus of
14. Barnard ND (2010) Trends in food availability, amygdala or PVN: neural dissociation of diet
1909–2007. Am J Clin Nutr 91:1530–1536 and energy. Am J Physiol 279:R86–92
15. Lenoir M et al (2007) Intense sweetness sur- 32. Hetherington MM et al (2000) Effects of acute
passes cocaine reward. PLoS One 2:e698 food deprivation on eating behavior in eating
16. Oswald KD et al (2010) Motivation for palat- disorders. Int J Eat Disord 28:272–283
able food despite consequences in an animal 33. Walsh BT et al (1989) Eating behavior of women
model of binge-eating. Int J Eat Disord 44: with bulimia. Arch Gen Psychiatry 46:54–58
203–211 34. Hagan MM et al (2002) Incidence of chaotic
17. Klump KL et al (2011) Binge eating proneness eating behaviors in binge-eating disorder: con-
emerges during puberty in female rats: a longi- tributing factors. Behav Med 28:99–105
tudinal study. J Abnorm Psychol 120:948–955 35. Wolff GE et al (2000) Differences in daily
18. Bulik CM, Sullivan PF, Kendler KS (2003) stress, mood, coping, and eating behavior in
Genetic and environmental contributions to binge eating and nonbinge eating college
obesity and binge eating. Int J Eat Disord women. Addict Behav 25:205–216
33:293–298 36. Cattanach L, Malley R, Rodin J (1988)
19. Hudson JI et al (2006) Binge-eating disorder Psychologic and physiologic reactivity to stres-
as a distinct familial phenotype in obese indi- sors in eating disordered individuals. Psychosom
viduals. Arch Gen Psychiatry 63:313–319 Med 50:591–599
20. Boggiano MM et al (2009) The Pavlovian 37. Laessle RG, Schulz S (2009) Stress-induced labo-
power of palatable food: lessons for weight-loss ratory eating behavior in obese women with binge
adherence from a new rodent model of cue- eating disorder. Int J Eat Disord 42:505–510
induced overeating. Int J Obes 33:693–701 38. Goldfield GS et al (2008) Stress and the rela-
21. Klump KL et al (2011) The effects of ovariec- tive reinforcing value of food in female binge
tomy on binge eating proneness in adult female eaters. Physiol Behav 93:579–587
rats. Horm Behav 59:585–593 39. Bohon C, Stice E, Burton E (2009) Maintenance
22. Boggiano MM, Chandler PC (2006) Binge eat- factors for persistence of bulimic pathology: a
ing in rats produced by combining dieting with prospective natural history study. Int J Eat
stress. Curr Protoc Neurosci Ch. 9, Unit 9.23A Disord 42:173–178
23. Boggiano MM et al (2005) Combined dieting 40. Perez M, Warren CS (2011) The relationship
and stress evoke exaggerated responses to opi- between quality of life, binge-eating disorder,
oids in binge-eating rats. Behav Neurosci 119: and obesity status in an ethnically diverse sam-
1207–1214 ple. Obesity 20:879–885
24. Hagan MM et al (2002) A new animal model of 41. Davis C, Carter JC (2009) Compulsive over-
binge-eating: key synergistic role of past caloric eating as an addiction disorder. A review of
restriction and stress. Physiol Behav 77:45–54 theory and evidence. Appetite 53:1–8
25. Hagan MM et al (2003) The role of palatable 42. Goldschmidt AB et al (2011) Eating disorder
food and hunger as trigger factors in an animal symptomatology in normal-weight vs. obese
model of stress induced binge-eating. Int J Eat individuals with binge eating disorder. Obesity
Disord 34:183–197 19:1515–1518
26. Robbins TW, Fray PJ (1980) Stress-induced 43. Bulik CM (2002) Eating disorders in adolescents
eating: fact, fiction or misunderstanding? and young adults. Child Adolesc Psychiatr Clin
Appetite 1:103–133 11:201–218
27. Donohoe TP (1984) Stress-induced anorexia: 44. Bassareo V, De Luca MA, Di Chiara G (2002)
implications for anorexia nervosa. Life Sci 34: Differential expression of motivational stimulus
203–218 properties by dopamine in nucleus accumbens
 2 Binge-Prone Versus Binge-Resistant Rats 25

shell versus core and prefrontal cortex. J Neurosci male rats from weaning to maturity. Physiol
22:4709–4719 Behav 50:1167–1174
45. Cifani C et al (2009) A preclinical model of 48. Drewnowski A et al (1992) Food preferences
binge eating elicited by yo-yo dieting and in human obesity: carbohydrates versus fats.
stressful exposure to food: effect of sibutramine, Appetite 18:207–221
fluoxetine, topiramate, and midazolam. 49. Wansink B, Cheney MM, Chan N (2003)
Psychopharmacology 204:1113–1115 Exploring comfort food preferences across age
46. Corwin RL, Avena NM, Boggiano MM (2011) and gender. Physiol Behav 79:739–747
Feeding and reward: perspectives from three 50. Consoli D et al (2009) Binge-like eating in
rat models of binge eating. Physiol Behav 104: mice. Int J Eat Disord 42:402–408
87–97 51. Nobel Foundation. Nobel Lectures, Physiology
47. Leibowitz SF et al (1991) Developmental pat- or Medicine. Amsterdam: Elsevier Publishing
terns of macronutrient intake in female and Company, 1967
 Chapter 3

Binge Eating in Female Rats Induced by Yo-Yo

Dieting and Stress
Carlo Cifani, Maria Vittoria Micioni Di Bonaventura,
Roberto Ciccocioppo, and Maurizio Massi

Abstract
Preclinical models are needed to investigate the neuro- and psycho-biology of binge eating (BE) and to
identify innovative pharmacotherapeutic strategies. A new model, based on the combination of cyclic
caloric restriction and acute stress, has been recently developed in our laboratory to induce BE of highly
palatable food (HPF) in female rats. Rats were exposed to three cycles of food restriction/refeeding and
then stressed on the test day. Acute stress was elicited by exposing rats to HPF, but preventing them from
accessing it for 15 min. This experimental procedure induces a marked binge-type intake of HPF.
Interestingly, in this model BE does not occur during the estrus phase of the ovarian cycle; if data from
female rats in estrus are not included in the statistical analysis, the variability of the BE response is very low.
Topiramate, sibutramine, and fluoxetine potently inhibited HPF intake in this model, providing evidence
for its predictive validity. The model has been used to investigate the effect of drugs targeting stress mecha-
nisms. The corticotrophin-releasing factor (CRF)-1 receptor antagonist R121919 selectively inhibited BE,
indicating that CRF is involved in the BE response. Its effect is likely exerted in extra-hypothalamic sites
rather than in hypothalamic sites controlling the hypothalamic–pituitary–adrenal axis. In addition, orexin-1
receptor antagonists selectivity inhibit BE; studies are under way to evaluate whether their effects are
related to influences on stress or on reward mechanisms. This preclinical model appears to be highly reli-
able and reproducible; it may represent a valid model to identify novel pharmacological treatments of BE
disorder and bulimia nervosa.

Key words: Binge eating, Stress, Food restriction, Highly palatable food, Female rats, Ovarian cycle,
CRF-1 receptor antagonists, Orexin receptor antagonists

1. Introduction

1.1. Background Episodes of binge eating (BE) in humans are characterized by

Information compulsive, nonhomeostatic consumption of an unusually large
quantity of highly palatable food (HPF) in a short period of time.
Even though not hungry, subjects eat more rapidly than normal

Nicole M. Avena (ed.), Animal Models of Eating Disorders, Neuromethods, vol. 74,
DOI 10.1007/978-1-62703-104-2_3, © Springer Science+Business Media, LLC 2013

27
28 C. Cifani et al.

until feeling uncomfortably full. As described by the DMS-IV-TR

(1), these episodes are accompanied by a subjective sense of loss of
control over eating, and are associated with feelings of distress,
disgust, depression, being guilty about overeating and eating alone
because of embarrassment.
BE represents a central feature of bulimia nervosa (BN), in
which episodes of BE are followed by behaviors aimed at avoiding
weight gain, such as self-induced vomiting. Intense and persistent
BE episodes represent a typical phenomenon occurring also in sub-
jects suffering from binge-eating disorder (BED) (2). BED,
described for the first time by A.J. Stunkard (3), is probably the
most prevalent eating disorder (4). It is characterized by repeated
episodes of BE in the absence of compensatory behaviors to avoid
weight gain. The DMS-IV-TR (1) indicates that among diagnostic
criteria for BED, BE episodes should occur at least 2 days per week
for 6 months. BED is associated with significant medical and psy-
chiatric comorbidity (5–7). It is estimated that BE afflicts approxi-
mately 5% of the US adult population at some time in their life (8)
and it contributes to obesity and associated pathologies (4, 9–11).
Medications that have been reported to reduce BE in clinical
studies, like topiramate (12, 13) or sibutramine (14–16), are associ-
ated with a variety of adverse side effects, which represent a serious
problem during chronic treatment (13, 17, 18). For example,
sibutramine, due to increased risks of serious cardiovascular side
effects, has been recently withdrawn from the European market.
Fluoxetine has been approved by the Food and Drug Administration
for BN, but evidence for its efficacy is inconclusive (19). Treatment
of BED and BN cannot simply rely on pharmacological agents aimed
at reducing food intake in general (i.e., serotonergic drugs). Hence,
BED and BN represent a still largely unmet medical need. In this
regard, our research group has activated a research program with the
aim to develop new pharmacological treatments for BED and BN.

1.2. Existing To date, several preclinical models to study the neuro- and psycho-
Experimental biology of BE have been proposed (see for review (20)), and these
Models of BE models have been used in attempts to develop innovative pharma-
cological treatments. A large body of evidence suggests that diet-
ing, stress, and negative affective states represent possible triggers
of BE in patients (21, 22). Indeed, dieting periods are a common
finding in the history of binge eaters, although hunger per se
appears not to be enough to induce BE in the absence of stress and
negative affective state (23, 24). Considerable evidence suggests
that BE may be caused by a unique interaction between dieting
and stress; thus, a history of cyclic food restriction and of environ-
mental stress may be responsible for its precipitation and mainte-
nance (25–27). Accordingly, recurring food restriction is
consistently the strongest predictor of overeating in response to
stress (21). Also typical of BE in humans is the preference for HPF.
 3 Binge Eating in Female Rats 29

Craving, preferential selection, and ultimate overconsumption of

HPF are common in BE disorders (28) and are considered to play
an important binge-triggering role in animal models (20, 29, 30).
In line with the hypothesis that dieting and stress are key etio-
logical determinants of BE (4, 22), the model proposed by Boggiano
and colleagues (and described in Chap. 2) (31–33), combines cycles
of food restriction/refeeding and acute stress to evoke BE for sweet
HPF. In this model, rats are submitted to cyclic caloric restriction
and stressed with electric foot-shock; stress is delivered to animals
that are not energy deficient, in keeping with the idea that BE epi-
sodes usually occur in conditions of satiety and normal body weight
(34). Rats are submitted to three consecutive 8-day cycles of food
restriction/refeeding, followed by the final test on day 25, since the
hyperphagic response to stress was found to be contingent upon a
minimum of three cycles. In response to stress, a selective increase
in HPF intake over chow is observed. Rats, which cycled through
food restriction and refeeding, in response to stress, fail to show
hyperphagia when only chow is available.
Several epidemiologic studies suggest that BE episodes are more
common in females than in males (1, 4, 35–37). American women
are approximately one-and-a-half times more likely to develop BED
than men, and they are three times more likely to develop BN than
men (4). In Norway, the female-to-male ratio is 1.7:1 for lifetime
prevalence of BED, and 3:1 for lifetime prevalence of BN in adoles-
cents (37). In consideration of the higher prevalence of BE in ado-
lescent and young adult women, young female rats are used. This
method is considered to have strong construct validity and face
validity as an isomorphic model (38) that presents elements of simi-
larity with the human symptomatology (20, 33).

2. Materials
and Procedures
A new experimental model of BE was recently developed in our
laboratory, modifying the Boggiano model, and aiming to increase
its reliability and face validity (39).

2.1. The Stressful The most relevant change compared to the Boggiano model was
Procedure related to the stressful procedure. In our previous studies concern-
ing stress-induced reinstatement of alcohol-seeking behavior (40),
large variability in the sensitivity of rats to electric foot-shock was
observed; animals highly sensitive to this stressful procedure exhib-
ited freezing behavior that prevented them from engaging in inges-
tive behavior. Several reports have shown that electric foot-shock
suppresses food intake (41), and in a few instances it has been
reported to induce either no effect or a small increase in intake (42,
43). Thus, electric foot-shock stress was substituted with a stressful
30 C. Cifani et al.

Fig. 1. The stressful procedure: rats were prevented from accessing HPF, but were able to
see and smell it.

procedure characterized by exposure of the animals to HPF, but

preventing them from accessing it. On the test day, animals were
prevented from getting access to HPF for 15 min before testing,
even though they were able to see and smell it (Fig. 1). This expe-
dient was adopted to generate a mild stressful condition character-
ized by a temporary lack of control over the environmental
circumstances (39).
In this 15 min period, rats engaged in repeated movements of
the forepaws, head, and trunk aimed at obtaining the HPF without
being able to reach it. Rats underwent the stressful procedure
between 1000 and 1200 hours. After 15 min, the cup was placed
inside the cage, so that HPF became accessible to the stressed rats.
As shown in Fig. 2, exposure to HPF without access to it,
increased corticosterone (CORT) levels in serum samples obtained
from rats sacrificed 15 min after the beginning of the stressful pro-
cedure, both in rats submitted to food restriction (R + S) and in rats
not submitted to food restriction (NR + S). These findings provide
evidence that the procedure was indeed able to evoke a stressful
response in the animals. This response was rather short lasting,
since 60 min after removal of the HPF cups from the wall of the
cage (without allowing the rats to access HPF), CORT levels
returned to control (NR + NS) levels.
This type of stress offers several advantages over the electric
foot-shock stress. First, it is a mild stress that, unlike the electric
 3 Binge Eating in Female Rats 31

90
**
80 **

Serum Corticosterone (ng/ml)

70

60

50

40

30

20

10

0
NR + NS NR + S R+S

Fig. 2. CORT levels in control rats (NR + NS ) and in rats exposed to stress with (R + S ) or
without (NR + S ) cycles of food restrictions. In R + S and NR + S rats CORT levels were
measured 15 min after the beginning of the stressful procedure. The values shown are the
mean ± SEM. Statistical differences from controls (NR + NS ): **p < 0.01.

foot-shock, never induces fear and freezing, but elicits a robust

behavioral activation. Second, the stressful experience implies a
relationship with HPF that resembles the approach-avoidance
stress over “forbidden” food that is very common among human
binge eaters, thus providing a further element of face validity.

2.2. The HPF Rather that using sweet biscuits, which usually generate a large
amount of spillage, a HPF formulated as a paste was employed. It
was obtained by mixing (a) Nutella (Ferrero, Alba, Torino, Italy)
chocolate cream (5.33 kcal/g; 56%, 31%, and 7% from carbohy-
drate, fat, and protein, respectively), (b) grounded food pellets
4RF18 (Mucedola, Settimo Milanese, Italy), and (c) water in the
following percent ratio: 52% Nutella, 33% food pellets, 15% water.
Rats exhibited a pronounced intake of HPF, since the first expo-
sure to it on day 5 of the first cycle (about 5.5 g per rat); the intake
increased on the following day (about 9 g per rat). On days 13 and
14 of the second cycle HPF intake did not increase further.

2.3. The Experimental Before tests, female rats were divided into four weight-matched
Procedure experimental groups (usually N = 9 per group):
Group 1: nonrestricted and not exposed to stress (NR + NS)
Group 2: restricted and not exposed to stress (R + NS)
Group 3: nonrestricted and exposed to stress (NR + S)
Group 4: restricted and exposed to stress (R + S)
Rats were maintained on 3 consecutive 8-day cycles, followed
by the final test on day 25, as follows:
32 C. Cifani et al.

270 NR + NS
NR + S
260 R + NS
R+S
250

Body Weight (g)

240

230

220

210

200
0 5 10 15 20 25
Days

Fig. 3. Effect of the three restriction/refeeding cycles on body weight (g) of the four groups
of female rats. The values are the mean ± SEM.
Rats in Group 1 (NR + NS), the control group, had ad libitum
access to chow for 4 days, on days 5–6 they received chow ad
libitum + HPF for 2 h; on days 7–8 they had chow ad libitum;
on day 25 they were not exposed to stress.
Rats in Group 2 (R + NS) had chow restricted to 66% of the normal
intake for 4 days; they were offered chow ad libitum and HPF
for 2 h on days 5–6, and only chow on days 7–8; on day 25
they were not exposed to stress. Restriction to 66% of normal
chow intake was defined for the first cycle on the basis of the
intake measured in the 6 days before the beginning of the
experiment. For the second and third cycle, 66% restriction
was defined on the basis of the intake of nonrestricted rats dur-
ing the last 2 days of the cycles, in which rats received only
normal chow ad libitum.
Rats in Group 3 (NR + S) had chow and HPF as controls, but were
exposed to stress on the test day (day 25).
Rats in Group 4 (R + S) had food available similar to Group 2, but
were exposed to stress on day 25.
The 8-day cycle was repeated three times, but in the third cycle
the animals did not have access to HPF on days 21 and 22. On day
25, free access to HPF and chow was offered and the intake was
measured in the first 2 h, taking care to collect any spillage. A mini-
mum of three caloric-restriction and refeeding cycles were run, as
in previous studies (31–33).
Body weights and food intake were recorded daily. Food intake
was expressed as the mean kcal/kg ingested ± S.E.M. By the last
day of refeeding, body weight and food intake of restricted rats
were not statistically different from those of nonrestricted rats
(Fig. 3), thus eliminating the potentially confounding influence of
hunger or energy deficit.
 3 Binge Eating in Female Rats 33

3. Anticipated
Results and Notes
3.1. Anticipated The experiments were initially carried out in four different groups
Results of rats; the overall ANOVA revealed a statistically significant differ-
ence in 2-h HPF intake in the different groups of rats in all of the
experiments.
As shown in Fig. 4, HPF intake in the R + S group was mark-
edly higher than in the control (NR + NS) group at the different
times of observation. The intake of HPF by R + S rats began imme-
diately after access to it; these animals never engaged in competing
behaviors, but continuously remained over the cup containing
HPF and focused their attention on its intake. HPF intake was very
pronounced in the first 15 min of access to it. After the first 15 min,
the additional intake of the four groups was similar, thus at 2 h the
cumulative intake of the R + S group remained higher than that of
the other groups. HPF intake of the groups NR + S or R + NS were
neither significantly different from that of controls. As far as the
intake of food pellets is concerned, the ANOVA revealed no
significant difference among groups. The intake of food pellets was
affected neither by food restriction, stress, nor the combination of
both.
The rats’ body weights were markedly reduced during the 4
days of food restriction, but rapidly recovered to levels of controls
by the end of each cycle. On the test day, the body weights of the
four groups of animals, as well as their food intake in the previous
24 h, were not statistically different.

180 ** *
160 **
140
**
HPF Intake (kcal/kg)

120

100
80 NR + NS
60 NR + S
R + NS
40 R+S
20

0
15 30 60 120
Time (min)

Fig. 4. HPF intake at different times after access to it on the test day (day 25). The values
shown are the mean ± SEM. Statistical differences from controls (NR + NS ): *p < 0.05;
**p < 0.01; where not indicated, the difference was not statistically significant.
34 C. Cifani et al.

Although the ANOVA gave a statistically significant effect in

all the experiments carried out with this model, a considerable
interanimal variability was evident: while in some animals the
increase in HPF was very pronounced, almost doubling the intake
of NR + NS rats, a small percentage of rats had a HPF intake strictly
similar to that of NR + NS animals.

3.2. Influence of the Searching for the reasons accounting for the observed variability,
Ovarian Cycle in This we thought it would be interesting to evaluate whether it might be
Model of BE related to the ovarian cycle of the female rats. Indeed, menstrual
cycle and gonadal hormones are known to influence eating behav-
ior in healthy females. Reductions in food intake and meal size
occur in the peri-ovulatory phase, following the rise of estradiol
secretion, while food intake generally increases in the luteal phase,
when plasma progesterone levels are high (44–47).
A large body of evidence shows a significant association
between changes in ovarian hormone levels and BE episodes dur-
ing the menstrual cycle in women with BN. For instance, several
studies have found an increased number of BE episodes in the pre-
menstrual compared to the menstrual period (48–50). Moreover,
a relatively recent longitudinal study reported that the increase in
estradiol and decrease in progesterone prospectively predict reduc-
tion of binge frequency (51). This negative association has been
replicated by Klump et al. (52) in two community samples of
women, in which decreases in estrogens were associated with over-
eating and greater likelihood of feeling “out of control.”
The ovarian hormone estradiol is involved in the physiological
control of feeding via interactions with anorexigenic peptides like
cholecystokinin (53–58), insulin, and leptin (59), as well as with orex-
igenic peptides like neuropeptide Y (60–62), ghrelin (63–65), and
melanin-concentrating hormone (66, 67). Estradiol also influences
serotonin release and degradation, as well as activation of its receptors
(68). Estrogens modulate dopaminergic systems, and this modula-
tion may involve environmental estrogen exposure (69).
In female rats, the estrous cycle is usually 4 days in length, with
four distinct phases (70):
1. Proestrus (P): estradiol rises to the highest levels and proges-
terone levels are low at the beginning and rapidly rise and
descend toward the end.
2. Estrus (E): estradiol and progesterone levels rapidly decline.
3. Metestrus (D1): estradiol levels are low and progesterone levels
begin to rise.
4. Diestrus (D2): estradiol levels are rising and progesterone
levels decline.
During the estrus phase rats, like other animals, show a tran-
sient decrease in food intake while they eat most during the diestrus
 3 Binge Eating in Female Rats 35

phase (71, 72). Most physiological estradiol effects have a latency

of 12 h or more, ~30 h in the study by Asarian and Geary (73),
since the activation of estrogen receptors stimulates transcription
factors. Therefore, decreases in food intake during the estrus phase
may be caused by the preceding increase in estradiol secretion in
the proestrus phase.
Bilateral ovariectomy (OVX) produces a rapid increase in food
intake, body weight, and adiposity (74, 75), removing estrogen’s
inhibitory effect. These responses to OVX can be normalized by a
regimen of estradiol treatment with a single subcutaneous injec-
tion of estradiol (76) that produces hormonal changes in plasma
similar to those observed in cycling rats. Estrogens regulate body
adiposity and fat distribution through the ER alpha (ERα) and
beta (ERβ) receptors (77, 78). However, only ERα has been pro-
posed to have a major influence on energy homeostasis (79). The
effects of estradiol on food intake appear to be mediated by ER
within the hypothalamus, particularly ventromedial and paraven-
tricular nucleus (PVN) (54, 65, 80).
Little is known about the role of estrogens on BE in rats. Yu
et al. (81) have shown that estradiol reduces binge size in female
rats, in which a highly restricted schedule of access to fat led to
binge-like intake of fat in a 1-h test. However, this effect was evi-
dent at the start of the study but not at the end, when bingeing was
fully established.
In our study, the ovarian cycle was monitored by examination
of vaginal smears obtained with a moistened cotton swab and warm
physiological saline; afterwards, the samples were transferred onto
glass slides for microscopic analysis. Following examination of vag-
inal smears on the test day, immediately after the HPF intake test,
statistical analysis revealed that HPF intake was significantly lower
during the estrus phase both in NR + NS and R + S rats (82). HPF
intake of R + S rats was significantly higher than that of NR + NS
rats during proestrus, metaestrus, and diestrus; however, during
estrus it was only slightly higher in R + S rats, and the difference
between the two groups was not statistically significant (Fig. 5).
These findings indicate that BE in our model does not occur dur-
ing the estrus phase and that the observed variability in the BE
response can be almost completely abolished if female rats in estrus
are not included in the statistical evaluation. These findings encour-
age further investigations of the mechanisms by which ovarian hor-
mones, particularly estradiol, control BE.

3.3. Drugs so Far To test the predictive validity of this preclinical model of BE, the
Tested in This Model following three drugs have been tested: sibutramine, fluoxetine,
and topiramate. They were chosen because clinical studies have
3.3.1. Drugs to Evaluate
reported that they may be effective in the treatment of bingeing-
the Predictive Validity
related eating disorders (12–17, 83–88). Sibutramine (Reductil®)
of the Model
is a centrally acting serotonin–noradrenaline reuptake inhibitor,
36 C. Cifani et al.

NR + NS
160
** * ** R+S
140

15 min HPF Intake (kcal/kg)

120

100

80

60

40

20

0
D1 D2 P E
Ovarian Cycle

Fig. 5. HPF intake on the test day (day 25) in R + S and in NR + NS female rats in the different
phases of the ovarian cycle: D1 (Metestrus), D2 (Diestrus), P (Proestrus), E (Estrus). The
values shown are the mean ± SEM. Statistical differences from controls (NR + NS ):
*p < 0.05, **p < 0.01; where not indicated, the difference was not statistically significant.

which has been reported to reduce food intake and to increase

energy expenditure (89). Fluoxetine (Prozac®) is a selective serotonin
reuptake inhibitor; it reduces food intake by affecting appetite and
satiety. In addition, fluoxetine appears to have positive effects on
the control of impulsive and compulsive symptoms associated with
psychiatric conditions like obsessive–compulsive disorder, BN, and
hypochondriasis (86). Topiramate (Topamax®) was developed as
an antiepileptic drug; however, clinical trials have shown that it
inhibits BE (12, 13). Sibutramine reduced HPF intake not only in
the R + S, but also in the other experimental groups, suggesting
that it exerts a rather general inhibitory effect on food consump-
tion. Fluoxetine, at the intragastric dose of 3 mg/kg, significantly
reduced HPF intake only in the R + S group. At the dose of 10 mg/
kg, the effect of fluoxetine was not selective and it significantly
reduced HPF intake in all four groups. On the other hand, topira-
mate, even at the highest dose (60 mg/kg) given by gavage, selec-
tively reduced HPF intake only in R + S rats.
These findings, particularly those obtained with topiramate,
suggest that the preclinical model described by Cifani et al. (39)
exhibits interesting elements of predictive validity. In addition, fur-
ther elements of face validity for this model derive from the finding
that the occurrence of BE in the female rats employed is influenced
by the ovarian cycle, as it happens in women.

3.3.2. Drugs Targeting As stated above, a large body of evidence suggests that stress may
Stress Mechanisms represent a key determinant of BE in patients suffering from BED
or BN (21, 22). The important role of stress in the etiology of BE
is emphasized by the finding that obese individuals with BED
 Another Random Document on
Scribd Without Any Related Topics
 Dies Boreales.
No. VIII.
CHRISTOPHER UNDER CANVASS.
Camp at Cladich.
Scene—The Wren's Nest.
Time—Evening.
North—Talboys—Seward—Buller.

NORTH.
Have you dined?
TALBOYS.
That we have, sir.
NORTH.
With me this has been Fast-day.
TALBOYS.
We saw it was, at our breakfast. Your abstinence at that meal, and
at luncheon, we knew from the composure of your features, and
your benignant silence, was not from any disorder of material
organisation, but from steady moral resolve; so his absence from the
Dinner-Table gave us no uneasiness about Numa.
NORTH.
No Nymph has been with him in the Grot.
 TALBOYS.
His Good Genius is always with him in Solitude. The form we
observed stealing—no, not stealing—gliding away—was, I verily
believe, but the Lady of the Wood.
NORTH.
The Glen, you know, is haunted; and sometimes when the green
umbrage is beginning to look grey in the still evening, I have more
than a glimpse of the Faery Queen.
SEWARD.
Perhaps we intrude on your dreams. Let us retire.
NORTH.
Take your seats. What Book is that, beneath your arm, Talboys?
TALBOYS.
The Volume you bid me bring with me this Evening to the Wren's
Nest.
NORTH.
Yes, yes—now I remember. You are here by appointment.
TALBOYS.
Else had we not been here. We had not merely your permission, sir
—but your invitation.
NORTH.
I was expecting you—and by hands unseen this our Round Table has
been spread for my guests. Pretty coffee-cups, are they not? Ask no
questions—there they are—but handle them gently—for the
porcelain is delicate—and at rude touch will disappear from your
fingers. A Book. Ay, ay—a Quarto—and by a writer of deserved
Fame.
SEWARD.
We are dissatisfied with it, sir. Dugald Stewart is hard on the Poet,
and we desire to hear a vindication from our Master's lips.
NORTH.
Master! We are all pupils Of the Poet. He is the Master of us all.
Talboys, read out—and begin at the beginning.
TALBOYS.
"In entering on this subject, it is proper to observe, that the word
Poet is not here used in that restricted sense in which it is commonly
employed; but in its original acceptation of Maker, or Creator. In
plainer language, it is used to comprehend all those who devote
themselves to the culture of the Arts which are addressed to the
Imagination; and in whose minds it may be presumed Imagination
has acquired a more than ordinary sway over the other powers of
the Understanding. By using the word in such a latitude, we shall be
enabled to generalise the observations which might otherwise seem
applicable merely to the different classes of versifiers."
NORTH.
That Mr. Stewart should, as a Philosopher, mark the liberal and
magnanimous, and metaphysical large acceptation of the Name is
right and good. But look at his Note.
TALBOYS.
"For this latitude in the use of the word Poet, I may plead the
example of Bacon and d'Alembert, the former of whom (De Aug.
Scient., lib. xi. cap. 1) comprehends under Poetry all fables or
fictitious histories, whether in prose or verse; while the latter
includes in it painting, sculpture, architecture, music, and their
different divisions."
NORTH.
"I may plead the example" appears to me a somewhat pompous
expression to signify that you have (very properly) adopted one
doctrine of one of the wisest, and another of one of the ablest of
men. But he does not seem to know that d'Alembert might have
"pleaded the example" of Aristotle in "including painting, sculpture,"
&c. "Poetry," says the Stagyrite, "consists in imitation, and the
imitation may be by pictures, sculpture, and the like." It is μιμησις—
and it is Man's nature to rejoice in imitation—χαιρειν τοις μιμημασιν.
But a singular and illustrative trait in Mr Stewart's treatment of the
subject is, that though he thus, at the outset, enlarges the Poet into
the Painter, the Sculptor, &c., yet throughout the whole composition,
(I know not if an incidental word may anywhere occur as an
exception,) every point of the argument regards the Poet in words
and verse! In what frame of understanding could—did he put this
Head to these fragments of limbs?
BULLER.
In the name of the Prophet—Figs!
NORTH.
I am more than half disposed to hint an objection to the use of the
words "sway over the other powers." We should have said—and we
do say, "predominance amongst the other powers." I see in "sway"
two meanings: first, a right meaning, or truth, not well expressed; to
wit, in thinking poetically—for his art, whatever it may be—or out of
his art—the Poet's other faculties minister to his Imagination. She
reigns. They conform their operations to hers. This manner of
intellectual action happens in all men, more or less, oftener or
seldomer; in the Poet—of what Art soever—upon each occasion,
with much more decision and eminence, and more habitually. But
secondly, a wrong meaning, or error, is better expressed by the word
"sway," to wit, that Imagination in the Poet illegitimately overbears
the other intellectual powers, as judgment, attention, reflection,
memory, prudence. Now, you may say that every power that is given
in great strength, tends to overbear unduly the other powers. The
syllogistic faculty does—the faculty of observation does—memory
does—and so a power unbalanced may appear as a weakness—as
wealth ruins a fool. But in the just dispensation of nature every
power is a power, and to the mind which she constitutes for
greatness she gives balanced powers. Giving one in large measure—
say Imagination—she gives as large the directly antagonistic power
—say the Intellective, the Logical; or she balances by a mass of
powers. I suspect that the undue over-swaying was in Stewart's
mind, and has probably distorted his language. I know that Genius is
the combination of ten faculties.
SEWARD.
Our expectations were raised to a high pitch by such grandiloquent
announcement: and we have found in the Essay—which is
unscientific in form—has no method—makes no progress—and is
throughout a jumble,—not one bold or original thought.
BULLER.
Too much occupied with exposure of vulgar errors—and instances
beneath the matter in hand. Great part too—extra thesin.
SEWARD.
You expect great things from the title—the Idea of the Poet. You
then see that Mr Stewart after all does not intend this, but only
certain influences, moral and intellectual, of characteristic pursuits.
This, if rightly and fully done, would have involved the Idea—and so
a portraiture indirect and incidental—still the features and their
proportion. Instead of the Idea, you find—
BULLER.
I don't know what.
TALBOYS.
The reader is made unhappy, first, by defect, or the absence of
principal features—then by degradation, or the low contemplation—
and by the general tenor.
NORTH.
Why, perhaps, you had better return the Quarto to its shelf in the
Van. Yet 'twould be a pity, too, to do so. I am for always keeping our
engagements; and as we agreed to have a talk about the Section
this evening, let us have a talk. Read away, Talboys—at the very
next Paragraph.
TALBOYS.
"The culture of Imagination does not diminish our interest in human
life, but is extremely apt to inspire the mind with false conceptions
of it. As this faculty derives its chief gratification from picturing to
itself things more perfect than what exist, it has a tendency to exalt
our expectations above the level of our present condition, and
frequently produces a youth of enthusiastic hopes, while it stores up
disappointment and disgust for maturer years. In general, it is the
characteristic of a poetical mind to be sanguine in its prospects of
futurity—a disposition extremely useful when seconded by great
activity and industry, but which, when accompanied, as it too
frequently is, with indolence, and with an overweening self-conceit,
is the source of numberless misfortunes."
BULLER.
Why, all this is—
NORTH.
Stop. Read on, Talboys.
TALBOYS.
"A thoughtlessness and imprudence with respect to the future, and a
general imprudence in the conduct of life, has been often laid to the
charge of Poets. Horace represents them as too much engrossed
and intoxicated with their favourite pursuits to think of anything else
—
BULLER.
Leave out the quotation from old Flaccus—and go on.
TALBOYS.
"This carelessness about the goods of fortune is an infirmity very
naturally resulting from their studies, and is only to be cured by
years and experience; or by a combination—very rare, indeed—of
poetical genius with a more than ordinary share of that homely
endowment COMMON SENSE."
BULLER.
Speak louder—yet that might not be easy. I feel the want of an ear-
trumpet, for you do drop your voice so at the end of sentences.
TALBOYS.
"A few exceptions"—
BULLER.
Stentor's alive again—oh! that I were head over ears in a bale of
cotton.
TALBOYS.
"A few exceptions to these observations may undoubtedly be found,
but they are so very few, as, by their singularity, to confirm rather
than weaken the general fact. In proof of this, we need only appeal
to the sad details recorded by Dr Johnson in his Lives of the Poets."
BULLER.
Skip—skip—skip—
SEWARD.
Skip—skip—skip—
TALBOYS.
May I, sir?
NORTH.
You may.
TALBOYS.
"Considered in its moral effects on the mind, one of the most
unfortunate consequences to be apprehended from the cultivation of
a poetical talent, is its tendency, by cherishing a puerile and irritable
vanity, to weaken the force, and to impair the independence of
character. Whoever limits his exertions to the gratification of others,
whether by personal exhibition, as in the case of the actor and
mimic, or by those kinds of literary composition which are calculated
for no end but to please or to entertain, renders himself, in some
measure, dependent on their caprices and humours."
BULLER.
Skip—skip—skip—
TALBOYS.
"In all the other departments of literature besides, to please is only a
secondary object. It is the primary one of poetry. Hence that timidity
of temper, and restless and unmanly desire of praise, and that
dependence on the capricious applause of the multitude, which so
often detract from the personal dignity of those whose productions
do honour to human nature."
NORTH.
I don't quite understand what Mr Stewart means here by "the
culture of Imagination." I see three senses of the word. First, the
cultivation by the study of written Poetry and the poetical arts, and
of the poetry poured through the Universe—to those minds which
receive without producing—a legitimate process. Secondly, the
cultivation as in Edwin, Beattie's young Minstrel, the destined and
self-destining Poet—a legitimate process. And thirdly, the self-
indulgence of a mind which, more sensitive than volitive, more
imaginative than intellectual, more wilful than lawful, more self-
loving than others-loving—turns life into a long reverie—an
illegitimate process. Which of these three classes of minds does
Stewart speak of? Strong native imagination in a young powerful
enthusiastic mind, tutored by poetical studies, but whom the Muse
has not selected to the services of her shrine? Or the faculty as in
the Poet-born self-tutored, and now rushing into his own predestined
work? Or the soft-souled and indolent fainéant Dreamer of life?
Three totally distinct subjects for the contemplation of the
Philosopher, but that here seem to hover confusedly and at once
before our Philosopher.
BULLER.
By his chosen title of the Section, The POET, he was bound to speak
of him according to Bacon, d'Alembert, and Aristotle.
NORTH.
The word culture must, I think, here specifically touch the First Case.
Shall we then be afraid of giving a share, and a large share too, to
the reading of the Poets, and the regard of the Fine Arts, in a liberal
Education? Poetry, History, Science, are the three strands of the
cable by which the vessel shall ride—Religion being the sheet-
anchor.
SEWARD.
Perhaps it is meant to touch the Second Case too?
NORTH.
It may be meant to do so, but it does not. The word "culture" is
dictated by or is proper to the First Case—for culture is deliberate
and elective. But in him—the young Poet—the Edwin—in whom
imagination is given in the measure assigned by the Muse to her
children, the culture proceeds undeliberate and unwilled. Edwin,
when he roves "beneath the precipice o'erhung with pine," or sitting
to watch the "wide-weltering waves," or is seized from the hint of
ballad or tale, or any chance word, with dreams and visions of the
more illustrious Past—follows a delight and desire that have the
nature and may have the name of a passion. All this is involuntary to
the unforeseen result—but afterwards, when he has accepted his art
for a vocation, he more than any man deliberately cultivates. Has
the Philosopher, then, in mind only the third class, and do the
dangers of "the culture of imagination" apply to them only—"the
indolent fainéant dreamers of life?" If so, he not only forgets and
loses his subject, as announced by himself, but wastes words on one
altogether below it. "False conceptions of human life!" Here is an
equivocation which must be set right. "Conceptions of human life"
are here meant to apply to expectations of the honesty, gratitude,
virtue of the persons in general with whom you or I shall come in
contact in life. Good. The contemplation of human beings—men and
women—ideally drawn by the Poet lifts me too high—tinges hope in
me with enthusiasm, and prepares disappointment. So it has been
often said, and said truly. This is conception prospective and
personal; and more philosophically termed Expectation. But then
"conception of human life"—from the lip of a philosopher should
mean rather "intelligence of man's life." Now I repeat that only
through the Poet have you true intelligence of man's life—either
external or internal. In the Actual the Poet sees the Idea—just as a
Painter does in respect of the visible man. In the man set before him
He sees two men—the man that is and the man of whom at his
nativity was given the possibility to be. He reads cause and effect;
and sees what has hindered the possible from being. Who, excepting
the Poet, does this? And excepting this, what intelligence of man is
an intelligence?
SEWARD.
There are two world-Wisdoms. One, to know men, as for the most
part they will show themselves—commonly called Knowledge of the
World: one, to know them as God made them. I forget what it is
called. Possibly it has no name.
NORTH.
Observe, my dear Seward, the precise error of that expectation. It is
to believe the good more prevalent than it is. It is no
misunderstanding as to the constitution of the good. The good is;
and the important point of all is to know it, when you meet it. To be
cheated, by not apprehending the ill of a man, is a wound to your
purse, and when you at last apprehend, to your heart. To be cheated
by not apprehending the good of man is—death, which you bear in
yourself, and know it not.
SEWARD.
What is desired? Is it that we should go into the world with hope not
a whit wider and higher than the dimensions of the reality that we
are to encounter? I trow not.
NORTH.
Your hope will elect your own destiny—will shape it—will be it. There
are possibilities given of the nobler happinesses, as well as of the
nobler services; and your hope, faithful to itself, will reach and grasp
them. And only to such hope are they given. Moreover, in all men
there is under the mask of evil which the world has shaped on them,
the power inextinct which the Creator sowed there; and they may, if
they dare to believe in it, and know to call to it, bring it out with a
burst. But belief is the main ingredient of the spell, and hope is the
mother of belief.
TALBOYS.
The Poet has glorious apprehensions of human existence—visions of
men—visions of men's actions—visions of men's destinies. He
pitches his theory of the human world above reality—and that he
shall, in due season or before it, learn—to his great loss and to his
great gain. In the meanwhile do not speak of the temper in him, as
if you would upbraid him with it. Do not lay to his charge the
splendour of his powers and aspirations. Do not chide and rate him
for his virtues.
SEWARD.
"False conceptions!" a term essentially of depreciation and reproach.
They are not false, they are true. For they are faithful to the
vocation that lies upon the human beings; but they, the human
beings, are false, and their lives are false; falling short of those true
conceptions.
NORTH.
Well. He—the Poet—comes to the encounter. It is the trial set for
him by his stars—as it is the trial set for all great spirits. He finds
those who disappoint him, and those who do not. But, grant the
disappointment, rather. What shall he do? That which all great spirits
do—transfer the grandeur of his hopes, over which fate, fortune, and
the winds of heaven ruled, to his own purposes of which he is
master.
TALBOYS.
Why did not Mr Stewart say simply that the Poet—and the young
enthusiast of Poetry—thinks better of his fellows than they deserve,
and brings a faith to them which they will take good care to
disappoint? Why harp thus on the jarring string; torturing our ears,
and putting our souls out of tune?
NORTH.
Who doubts—who does not know, and admire, and love Hope—in
the ardent generous spirit—looking out from within the Eden of
Youth into the world into which it shall, alas! fall? What is asked?
That the spring-flowering of youth shall be prematurely blighted and
blasted by winds frosty or fiery, which the set fruit may bear? Of
course we hope beyond the reality, and it is God's gift that we do.
TALBOYS.
And why lay that Imagination which looks into Life with unmeasured
ideas to the charge of the Poet alone? Herein every man is a Poet,
more or less; and, most, every spirit of power—the hero, the saint,
the minister of religion, the very Philosopher. Would we ask, sir, for a
new law of nature? Upon the elements, fewer or more, which an
anticipated experience gathers, a spirit impelled by the yearnings
inseparable from self-conscious power, and mighty to create, works
unchecked and unruled. What shall it do but build glorious illusions?
NORTH.
"The culture of Imagination,"—understanding thereby, first, in the
Great Poets themselves, the intercourse of their own minds with
facts which imagination vivifies, and with ideas which it creates—of
humanity; and secondly, in all others, as poets to be or not to be,
the reading of the Great Poets, Mr Stewart says—"does not diminish
our interest in human life." Does not diminish! Quite the reverse. It
extraordinarily deepens and heightens, increases and ennobles. For
who are the painters, the authentic delineators and revealers of
human life, outer and inner—
BULLER.
Why, the Poets—the Poets to be sure—the Poets beyond all doubt—
NORTH.
"Extremely apt to inspire the mind with false conceptions of it"—and
so on. Why, the Faculty is there with a mission. It is its bounden
office—its embassy from heaven—to exalt us above our earthly
experience—to lift us into the ideal possibility of things. Thereby it is
an "angel of Life," the white-winged good genius. The too sanguine
hope is an adhering consequence, and the quelling of the hope is
one of the penalties which we pay for Adam and Eve's coming
through that Eastern Gate into this Lower World.
TALBOYS.
Of course, my dear sir, every power has its dangers—the greater, the
profounder, the more penetrating and vital the power, the greater
the danger. But is this the way that a Philosopher begins to treat of a
power—with hesitation and distrust—inauspiciously auspicating his
inquiry? The common—the better—the true order of treatment is by
Use and, Abuse—Use first. "Expectations above the level of our
present existence!" Of course—that when the heaven on earth fails,
we may have learnt "to expect above the level of our present
existence," and go on doing so more and more, till Earth shall fade
and Heaven open.
SEWARD.
"Frequently produces a youth of enthusiastic hope!" Is this proposed
as a perversion and calamity, a "youth" to be deprecated?
 NORTH.
I really don't know—it looks almost like it.
SEWARD.
Will you say Wo and Alas! for the City—Wo and Alas! for the Nation
—in which princes, and nobles, and the gentle of blood—and the
merchants, and the husbandmen, and the peasants, and the
artisans, suffer under this endemic and feverous malady—a "youth
of enthusiastic hope?" Methinks, sir, you would expect there to find
an overflow of Pericles's, and Pindars, and Phidias's, and
Shakspeares, and Chathams, and Wolfes—
BULLER.
Stop, Seward—spare us the Catalogue.
SEWARD.
You would say—here is the People that is to lead the world in Arms
and in Arts. Only let us use all our endeavours to see that the
community produces reason enough in balance of the enthusiasm.
BULLER.
Let us procure Aristotles, and Socrates's, and Newtons, and—
TALBOYS.
What should a Philosopher do or say relatively to any particular
power? He expounds an Economy of Nature. Therefore, he says, let
us look how Nature deals with such or such a power. She gives it for
such and such uses: and such is its fostering, and such are its
phenomena. But as every power unbalanced carries the subject in
which it inheres ex orbita, let us look how nature provides to balance
this power which we consider.
NORTH.
That, my dear Talboys, is a magnanimous and a capacious way of
inquiry. But how can any man write about a power who has not a
full sympathy with it? I have no doubt that Davy, when he wielded
Galvanism to make wonderful and beautiful revelations of veiled
things, deeply and largely sympathised with Galvanism. You would
think it easier to sympathise with Imagination, and yet to Stewart it
seems almost more difficult. Go on.
TALBOYS.
How has Nature dealt with her mighty and perilous power—Love.
Look at it, where it is raised to its despotism—when a man loves a
woman, and that woman that man. It is a power to unhinge a world.
Lo! in proof "an old song"—the Iliad!

'Trojanas ut opes et lamentabile regnum

Eruerint Danai!'

Has Nature feared, therefore, to use it? She builds the world with it.
And look how she proceeds. To these two—the Lovers as they are
called—the Universe is in these two—to each in the other. The rest
of the Universe is shut out from their view, or more wonderfully
comprehended in their view—seen to each through and relatively to
the other—seen transformed in the magical mirror of their love. Can
you expect anything less than that they should go by different doors,
or by the same door, into Bedlam? Lo! they have become a Father
and a Mother! They have returned into the real world—into a world
yet dearer than Dreamland! The world in which their children shall
grow up into men and women. Sedate, vigilant, circumspect,
sedulous, industrious, wise, just—Pater-familias and Mater-familias.
So Nature lets down from an Unreal which she has chosen, and
knows how to use.
NORTH.
The ground of the Poet, my dear Talboys, is an extraordinary
dotation of sensibility—of course, ten thousand dangers. Life is
exuberant in him—and if the world lies at all wide about him, the joy
of the great and the beautiful. The dearest of all interests to every
rational soul is her own coming destiny. The Poet, quick and keen
above all men in self-reference, must, among his contemplations and
creations, be full of contemplating and creating his own future, and
must pour over it all his power of joy, rosy and golden hopes. And
that vision, framed with all his power of the Ideal, must needs be
something exceedingly different from that which this bare, and
blank, and hard earth of reality has to bestow. What follows? A
severe, and perhaps an unprepared trial. The self-protection
demanded of him is a morally-guarded heart and life. The protection
provided for him is—his Art. The visions—the Ideal—the Great and
the Fair, which he cannot incorporate in his own straitened existence
—the ambitions, at large, of his imagination he localises—colonises—
imparadises—in his works. He has two lives; the life of his daily
steps upon the hard and bare, or the green, and elastic, and sweet-
smelling earth, and the life of his books, papers, and poetical,
studious reveries—art-intending, intellectual ecstasies.
BULLER.
What say you, sir, to the charge of "overweening self-conceit and
indolence?"
NORTH.
What say you, my Buller?
BULLER.
That I do not quite understand the proposition. Is it, that generally
the "sanguine" temperament is apt to make these accompaniments
for itself? Or that in the Poet the three elements are often found
together? If the former, I see no truth in it. The sanguine temper
should naturally inspire activity—and I do not quite know what is
here an "overweening conceit." That a sanguine-minded man is apt
to have great self-reliance in any project he has in hand—a
confidence in his own present views that is not a little refractory to
good argument of cooler observers, I understand. But that sort of
self-conceit which makes of a man an intellectual fop—gazing in the
pocket looking-glass of self-conceit at his own perfections—vain self-
contemplation and self-adulation—the sanguine temper is far more
likely to carry a man out of himself, to occupy his time, his pleasure,
and his passion in works, and withdraw them from himself. I
suppose, therefore, that we must look to the Poet alone. I daresay
that small poets have a great conceit of themselves. They have a
talent that is flattered and admired far beyond its worth. They
readily fancy themselves members of the Immortal Family. But a true
Poet has a thousand sources of humility. Does he not reverence all
greatness, moral and intellectual? Does he not reverence, above all,
the mighty masters of song? He understands their greatness—he
can measure distances—which your small Poet cannot.
NORTH.
Every soul conscious of power is in danger of estimating the power
too highly; but I do not know why the Poet should be so more than
another man. Then, what is "overweening?" Is it overvaluing himself
relatively to other men? Is it over-measuring his power of
achievement—whence disproportionate undertakings, that fail in
their accomplishment? I can more easily suppose that all the Sons of
Genius "overween" in this direction. They must needs shape
enterprises of unattainable magnificence. But some one has said
rightly that in attempting the Impossible we accomplish the Possible.
But this is a higher and truer and more generous meaning, I fancy,
than is intended by the choice of that slighting and scoffing dispraise
of "overweening"—a word pointing to a social, or moral, defect that
makes an exceedingly disagreeable companion, rather than to any
sublime error in the calculations of genius. And I come back upon
the small sinner in rhyme, who has been cockered by his friends and
cuddled by himself into conceit, till he thinks the world not good
enough for him—takes no trouble to satisfy Its reasonable
expectations, and finds that It will take none to satisfy his
unreasonable ones—there is a source of "numberless misfortunes"—
a seedy surtout, a faded vest, and very threadbare inexpressibles.
TALBOYS.
And why should those who are sanguine in hope be "too frequently
indolent?" A hopeful temper engender indolence! A desponding
temper engenders it; a hopeful one is the very spur of activity. The
sanguine spirit of hope taking possession of an active intellect,
engenders the Projector—of all human beings the most restless and
indefatigable—his undaunted and unconquerable trust in futurity
creates for itself incessantly new shapes of exertion—till the curtain
falls.
SEWARD.
There is, I suppose, a species of Castle-builder who hopes and does
nothing; as if he believed that futurity had the special charge of
bringing into existence the children of his wish. But his temper is not
properly called sanguine—it is dreamy. Neither is his indolence a
consequence of his dreams; but as much or more, his dreams, of his
indolence. He sits and dreams. Say that Nature has given to some
one, as she will from time to time, an active fancy and an indolent
humour—a disproportion in one faculty. 'Tis a misfortune: and a
reason why his friends should seek out, if possible, the means of
stirring him into activity; but it has nothing to do with describing the
Idea of the Poetical Character.
TALBOYS.
The Great Poets have not been indolent. They have been working
men. The genius of the Poet calls him to his work. Shakspeare was a
man of business. Spenser was a state-secretary.
BULLER.
Read Milton's Life.
TALBOYS.
See Cowper drowned in an invincible melancholy, and deliberately
choosing a long-lasting and severe task of his Art, as a means of
relieving, from hour to hour, the pressure of his intolerable burthen.
If he had drooped under his hopeless disease into motionless stupor,
you could not have wondered, much less could you have blamed. He
fought, pen in hand, year after year, against the still-repelled and
ultimately victorious enemy.
BULLER.
Think of Southey!
NORTH.
Yet the Poet is in danger of indolence. For in his younger years joy
comes to him unpurchased. To do, takes him out of his dream. To do
nothing, is to live in an enchanted world; and with all tenderness be
it said, he hath, too, his specific temptation to overmuch self-
esteem. Because his specific faculty and habit are to refer every
thing that befalls constantly to himself as a contemplative spirit.
Herein is the most luminous intuition alone. The perversion is to be
quick and keen in referring to the ignobler Self—for as I or you said,
and all men may know, the Poet assuredly has two souls. Personal
estimation, personal prospects! A sensibility to injury, to fear, to
harm, to misprision—a quick jealousy—suspicion—soreness! You do
see them in Poets—and in Artists, who after their kind are Poets—for
they are Men. As to excessive reflection upon and admiration of their
own intellectual powers, while we rightly condemn it, we should
remember that the Poet is gifted, and in comparison with most of
those with whom he lives, is in certain directions far abler; and more
delicate apprehensions he probably has than most or all of them—at
least of such apprehensions as come under the Pleasures of
Imagination. And when he begins to call auditors to his Harp—then,
well-a-day!—then he lives and feeds upon the breath of praise—and
upon the glow of sympathy—a flower that opens to the caress of
zephyrs and sunbeams, and without them pines. Then comes envy
and spiritual covetousness. Others obtain the praise and the
sympathy—others who merit them less, or not at all. What a
temptation to disparage all others—alive! And to the Poet, essentially
plunged in the individualities of his own being, how easy! For each
of his rivals has a different individuality from his own; and how easy
to construe points of difference into points of inferiority! Easy to him
whom pain wrings more than it does others—to whom disagreeable
things are more disagreeable—
TALBOYS.
Have done, sir, I beseech you, have done—talk not so of the
Brotherhood.
NORTH.
I am thinking of some of the most majestic!
SEWARD.
Alas! it is true.
NORTH.
Mr Stewart more than insinuates, with a wavering and equivocating
uncertainty of assertion he signifies, that the Poet, or poetic mind, is
not much endowed with "common sense." Talboys, what say you?
TALBOYS.
I rather think it unusually well-endowed that way, and that it is the
opposite class of minds—those that cultivate abstract science—that
have, or seem to have, least of it.
SEWARD.
The poetic mind, from its sensibility, is peculiarly ready to
sympathise with the general mind, and it is that sympathy that
produces common sense. Common sense is instinctive; and in its
origin allied to that which in the higher acts of the poet's mind is
called Inspiration. Therefore it is native to his mind. It is an
inspiration of his mind as much as poetic Imagination.
BULLER.
Has Seward said what you meant to say, Talboys?
TALBOYS.
He has—why did not you? But observe, Buller, common sense is not
solely employed upon a man's own conduct: it has all the world
besides for its object. The common sense of a Poet in his own case
may be disturbed by his sensibilities, which are greater than
common; while yet, in all other cases, it may be truer than the
magnet.
 BULLER.
Good.
TALBOYS.
I will trouble you, if you please, for an Obs.
BULLER.
I have long desired a definition of Common Sense. It seems to me
rather a commonplace thing. I suppose it is called Common Sense,
as being common to men, so that you may expect it in 9 out of 10,
or 99 out of 100.
TALBOYS.
Pretty good.
BULLER.
Common Life seems to be the school of it. It seems a practical
faculty, or to respect practice. Obvious relations are its domain—
obvious connexions of cause and effect—means and end. A man of
common sense effects a plain object, quickly and cheaply, by ready
and direct means. High reach of thought is distinguished from
common sense on the same side, as downright folly is on the other.
Yet the interests dealt with need not be, if they frequently are, low;
only the relations obvious. Perhaps the phrase is oftener brought out
by its violation than its maintenance. He who wants common sense
employs means thwarting his end. I propose that Common Sense is
a combination of common understanding and common experience.
TALBOYS.
I asked you, my dear Buller, for an Obs—one single Obs—you have
given us a dozen—a Series. Let us take them one by one, and
dissect the—
BULLER.
Be hanged if we do! I am afraid that my notion of Common Sense is
but a low one. I think that a blacksmith may acquire common sense
about shoeing of horses, and a housewife about her kitchen and
laundry. Sound sense applicable to high matters is another matter—
une toute autre chose.
TALBOYS.
Be done, dear Buller.
BULLER.
In a moment. Moreover, I can imagine a strong, clear, sound sense
confined to a special higher employment—a lawyer who would
manage the most difficult and hazardous cause with admirable
discretion, and make a mere fool of himself in marrying.
TALBOYS.
Be done—be done.
BULLER.
In a moment. I am not able to affirm that a Poet of high and sound
faculties must have the talent for conducting himself with prudence
in the common affairs of life; and really that is what seems to me to
be Common Sense.
TALBOYS.
Be done now—you cannot better it.
BULLER.
About the Poet what can I say that every body does not know and
say in all the weekly newspapers. Why, gentlemen, the Mission of
the Poet is to fight the fight of the Spirit against the flesh, and to
extend the reign of the Beautiful. Also, he is the Prophet of [Greek:
gnôthi seauton]: and the finest of wordmongers. The words that he
touches turn all to gold. He is the subtlest of thinkers. Our best
discipline of thinking has been from the Poets. Compare Shakspeare
and Euclid.
TALBOYS.
From you! Buller, you astonish me.
 BULLER.
Astonishment is sometimes proof of a weak mind.
NORTH.
There seem to be two Common Senses. Goldsmith appears to be
viewed as an eminent case of wanting it, in conduct—the practical—
for his own use. But the theoretical—for judging others—imaginary
cases—characterises that immortal work, The Vicar of Wakefield:
and the theoretical, for judging other men real, existing, and known,
his Retaliation. The criticism of Burke, for instance, is all exalted
Common Sense—

"Who, born for the Universe, narrowed his mind,

And to Party gave up what was meant for Mankind."

That is the larger grasp of common Sense rising into high Sense.

"And thought of convincing while they thought of

dining"

is its homelier scope.

SEWARD.
Common Sense is the lower part of complete Good Sense.
Shakspeare and Phidias must use Good Sense in governing their
whole composition; which Common Sense could not reach; and a
man might have good sense in composing a group in marble, yet
want it in governing his family. But Phidias executing a Venus with a
blunt notched chisel, would want Common Sense.
NORTH.
Wordsworth the Great and Good has said that "the privilege and the
duty of Poetry is to describe things not as they are, but as they
seem to the senses and the passions;" and when in so saying he
claimed further for the works of Poetry law and constancy, he spake
heroically and thence well,—up to the mark of the fearless and clear
truth. But when he condescended to speak of "one quality that is
always favourable to good poetry, namely, good sense," he said that,
without note of reserve, which should have been guarded. Good
sense, if you please, but such good sense as Homer shows when the
κλαγγη of the silver bow sounds—when the Mountain-Isle trembles
with all her Woods to Neptune stepping along—or the many-folded
snowy Olympus to Jupiter giving the one calm, slow, simple,
majestic, earth-and-heaven-obliging Nod—or when at the loosed
storm of terrestrial and celestial battle on the Scamandrian plain, the
Infernal Jove leaps from his throne, and shouts, or yells, or bellows
—μεγ' ιαχε—lest the solidly-vaulted Earth rend above and let in
sunlight on the Shades. The "good sense" of Shakspeare, when the
Witches mingle in the hell-broth "Tartar's lips," and "yew-slips
slivered in the Moon's eclipse." Claim the good sense, but claim it in
its own kind—separated and high—kingly—Delphic—divine. The
good sense of Jupiter—Apollo—the Nine Muses, and the practical
Pallas Athene. Or claim Wisdom—and not "good sense;"—"the meed
of Poets SAGE!" Lucid intelligence—profound intuitions—disclosed
essences—hidden relations laid bare—laws discerned—systems and
worlds comprehended—revealed mysteries—prophecy—the "terrible
sagacity"—and to all these add the circumspection—the caution—the
self-rule—the attentive and skilful prudence of consummate Art,
commanding effects which she forecast and willed. Wisdom in
choosing his aim—Wisdom in reaching his aim—Wisdom to weigh
men's minds and men's deeds—their hopes, fears, interests—to read
the leaves of the books which men have written—to read the leaves
of the book which the Creating Finger has written—to read the
leaves of the book which lies for ever open before the Three Sisters
—the leaves which the Storms of the Ages turn over.
TALBOYS.
Coffee, my dear sir? Here's a cup—cool and sweetened to your taste
to a nicety.
NORTH.
Thanks, Talboys. I am ready for another spell.
 BULLER.
Reflect, sir, breathe awhile. Do, Seward, interpose something
between the Master and exhaustion. Quick—quick—else he will be
off again—and at his time of Life—
SEWARD.
Oh for the gift denied me by my star—presence of mind!
TALBOYS.
Common sense, in a high philosophical signification, is the sum of
human opinions and feelings; or the "Universal Sense" of mankind.
That is not homely—and cannot therefore be what Stewart calls that
"homely endowment." The apter translation of the place in his Essay
is "ordinary sense or understanding"—which seems to suggest now
"so much sense or understanding as you ordinarily meet with among
men"—and now "sense and understanding applied to ordinary
concerns." Only this last makes the quality homely. But the tooth of
Stewart's insult is in the prior suggestion (in the case of the Gifted,
untrue), that they have not as much sense or understanding as you
ordinarily meet with. They have ten, twenty, a thousand times as
much. Think of Robert Burns! But they have—or may, I do not say
must have—the repugnance to apply the winged and "delighted
spirit" to considerations and cares that are easily felt as if sordid and
servile—imprisoning—odious. They suffer, however, not for the lack
of knowing, but of resolution to conform their doing to their
knowing. They sin against common sense—and much more against
their own. Hinc illæ lacrymæ.
NORTH.
Gentlemen, the Cardinal Virtue—Prudence—holds her sway, in the
world of man, over Action, and, as much as she may, over Event, by
the union as if of two Sceptres. For She must reign, at once, in the
Understanding and in the Will. Common Sense, as the word is
commonly meant and understood, is Intellectual Prudence applied to
the more obvious requisitions of the more obvious interests which
daily and hourly claim our concern and regard. This Intellectual
Prudence, thus applied—that is to say, the clear Intelligence of these
requisitions—Common Sense, therefore—one man has, and another
has not. The case shall occur that the man, Poet or no Poet, who
has it, shall act like a fool; whilst the Poet or no Poet, who has it not,
shall act like a Sage. For the man, wise to see and to know, shall
have yielded the throne of his Will to some usurping and tyrannising
desire—and the other, who either does not possess, or who
possessing, has not so applied the Intelligence—some dedicated
Mathematician, or Metaphysician, or Mechanician, or Naturalist, or
Scholar, or Antiquary, or Artist, or Poet, shall live wisely, because he
has brought his heart and his blood under the rule of Moral
Necessity. Prudence, or, in her stead, Conscience, has established
her reign in his Will. To be endowed with Common Sense is one
thing; to act with common sense, or agreeably to her demands, is
another. Popular speech—loose, negligent, self-willed, humoursome
and humorous—often poetical—easily and gladly confounds the two
neighbouring cases. Philosophic disquisition—which this of Dugald
Stewart does not—should sedulously hold them apart. You may
judge of a man's Common Sense by hearing him criticise the
character and conduct of his neighbour. To learn in what hand the
Sceptre of the Will is, you must enter his own doors. The proneness
of the Poet, easy, kind, frank—except in his Art, artless—
compassionate, generous, and, large-thoughted—heaven-aspiring—
to neglect, like the lover, (and what else is he but the perpetually
enthralled lover of the Good, the True, and the Beautiful?) the
earthly and distasteful Cura Peculî, is to be counteracted mainly on
the side of the Will. Simplicity of desire will go far, and this you may
expect in him from Nature—indeed it is the first ground of the fault
charged. Next, of stronger avail—not perhaps of more dignity—
comes that which is indeed the base, if not yet the edified structure
of Common Sense, the plain Intelligence of naked Necessity. No
great stretch of intellectual power required, surely, for discovering
and knowing his own condition in the work-day world! But the goods
of fortune—worldly estate—money—shall the "heavenly Essence"—
the "celestial Virtue"—the "divine Emanation"—for so loftily has Man
spoken of Man—that is within us—crouch down and grovel in this
dark, chill den—this grave which Mammon has delved to be to it a
pitfall and a prison?
BULLER.
Ay—why shall the Poet guard and noose the strings of his purse?
NORTH.
One reason, drawn from the sublimity of his being, stands ever nigh
to bow the pliant neck of his Will under the lowly yoke. He must—
because, according to the manner in which the All-Disposer saw
good to order and adjust the constituents and conditions of our
human life here below, in him who, of his own will and deed, lays
himself under a bond to live by unearned bread, the Moral Soul dies.
SEWARD.
The Poet is not—and he is—improvident. Nothing in his genius binds
him to improvidence. Prudence may accompany sensibility—may
accompany ample and soaring contemplations—may accompany
creative thought—may accompany the diligent observation of human
life and manners—may accompany profound insight into the human
heart. These are chief constituents of the poetical mind, and have
nothing in them that rejects Prudence.
BULLER.
Neither do I believe that the more distinguished Poets generally
have been culpably unforethinking—
 "Vatis avarus
Non temere est animus!"

I hope so. I should be exceedingly sorry to think that the Bard were
apt to give into the most odious of all vices. But the interval is wide
from vicious negligence to vicious care: and I hope that somewhere
between, and verging from the Golden Mean a little way towards the
negligent extreme, might be the proper and earned place of the
Poets.
TALBOYS.
We must confess to some negligent tendencies in the Poet. The
warm sympathies give advantage to designing beggars of different
ranks—and are themselves betraying advisers. The law of the
poetical mind to accept Impression, and let it have its way, if it
overflow its legitimate channel of poetical study and art, and
irregularly lay the conduct of life under water, may leave behind it
something else than fertility. The dwelling in pleasure may make the
narrow and exact cares of economy irksome. But why shall we
expect that a man of high, clear, and strong mind shall not learn
how to—cut his coat according to his cloth?
NORTH.
I am afraid that the high faculties of a Poet threaten to endanger his
vulgar welfare. The foundation of his poetical being and power, as
you well have hinted, Talboys, is the free spontaneity of motion in
his own mind—the surrendering of his whole spirit to influxes and
self-impulses. The spontaneous movement allies his temperament to
common passion, which founds upon this very characteristic. And
you sometimes see, accordingly, that the Poet is a victim sacrificed
for the benefit of the rest. Not that it need be so—for he has his own
means of protection; but powers delicate, sensitive, profound, must
walk perilously in a lapsed world.
SEWARD.
Let it be allowed, then, to Dugald, that the poetical temperament is
adverse to getting—and to keeping—money—and that a touching
picture might be drawn of the conflicts of spirit between a Poet and
his false position in a counting-house—or with "poverty's
unconquerable bar."
NORTH.
"This carelessness about the goods of fortune," says Mr Stewart, "is
an infirmity very naturally resulting from their studies, and is only to
be cured by years and experience, or by combination (very rare
indeed) of poetical genius with a more than ordinary share of that
'homely endowment called common-sense.'" And wherefore any
infirmity? Why not have portrayed rather—or at least kindly qualified
the word—in winning hues, or in lofty shape—the delicious or
magnanimous Unworldliness of the poetical character? That most
ennobling, and most unostentatious quality, which dear and great
Goddess—in lovingly tempering a soul that from its first inhalation of
terrestrial air to the breath in which it escapes home, she intends to
follow with her love—commingles in precious and perilous atoms
that, in consecrating, destine to sorrow.
SEWARD.
An infirmity? A charm—a grace—and a virtue! Alas! sir, a virtue too
suitable to the golden age to be safe in ours.
TALBOYS.
Ay, Seward, a virtue demanding the correction or the protection of
some others, which the iron generations countenance or allow—such
as Prudence, Justice, Affection for those whose welfare he
unavoidably commixes with his own.
NORTH.
Protection! It sometimes happily wins its protection from virtues that
love and admiration rouse and arm in other breasts, in its favour—a
reverent love—a pitying admiration.
TALBOYS.
Welcome to our website – the perfect destination for book lovers and
knowledge seekers. We believe that every book holds a new world,
offering opportunities for learning, discovery, and personal growth.
That’s why we are dedicated to bringing you a diverse collection of
books, ranging from classic literature and specialized publications to
self-development guides and children's books.

More than just a book-buying platform, we strive to be a bridge

connecting you with timeless cultural and intellectual values. With an
elegant, user-friendly interface and a smart search system, you can
quickly find the books that best suit your interests. Additionally,
our special promotions and home delivery services help you save time
and fully enjoy the joy of reading.

Join us on a journey of knowledge exploration, passion nurturing, and

personal growth every day!

ebookbell.com