Models of Mental Disorders: A New Comparative Psychiatry

199 Pages·1988·3.105 MB·English

by  William T. McKinney M.D. (auth.)

Models of
Mental Disorders
A New Comparative Psychiatry
Models of
Mental Disorders
A New Comparative Psychiatry
William T. McKinney, M.D.
University of Wisconsin Medical School
Madison, Wisconsin
PLENUM MEDICAL BOOK COMPANY
NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
McKinney, William T.
Models of mental disorders.
Includes bibliographies and index.
1. Mental Illness-Animal models. 2. Animal psychopathology. 3. Psychiatry,
Comparative. 1. Title. [DNLM: 1. Disease Models, Animal. 2. Mental Disorders. 3.
Psychopathology. WM l00M4784]
RC455.4.A54M35 1988 616.89'00724 88-2335
ISBN-13: 978-1-4684-5432-1 e-ISBN-13: 978-1-4684-5430-7
DOl: 10.1007/978-1-4684-5430-7
© 1988 Plenum Publishing Corporation
Softcover reprint of the hardcover 1st edition 1988
233 Spring Street, New York, N.Y. 10013
Plenum Medical Book Company is an imprint of Plenum Publishing Corporation
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Preface
My ideas for this book have been evolving over the last several years as I
have been working in the animal modeling area and have seen it change
rather dramatically. There have been tremendous advances, both in
methodology and in conceptualization, yet the literature is scattered in
journals encompassing many disciplines. In particular, there have been
only very limited attempts to write about the philosophical, conceptual,
and controversial issues in this field; to pull together diverse findings;
and to provide some general perspective on its future.
As will probably be apparent, I am a clinical psychiatrist who also
has a fundamental interest in animal behavior, especially primate social
behavior. I entered the field from a clinical research standpoint to devel
op some animal models of depression after being stimulated to do so by
Dr. William Bunney, then at the National Institute of Mental Health and
now at the University of California-Irvine. The field has grown rapidly
since then and there is considerable research activity. Indeed, the re
search activity has grown more rapidly than our conceptualization of
what animal models are and are not.
Animal preparations are now available for studying specific aspects
of certain types of psychopathology. Thoughtful workers in the animal
modeling field no longer talk about comprehensive models but rather
about more limited experimental preparations in animals for studying
certain specific aspects of human psychopathology.
Despite the amount of research activity in this area, there is no
integrated and easily available reference source for students and work
ers. This particular book is intended to be a discussion of some general
philosophical issues concerning the development, evaluation, and uses
of animal models in psychiatry, plus an overview of four selected areas
v
vi Preface
of research in the animal modeling field. It would be impossible to be
comprehensive and still have a book of manageable size. Rather, the
attempt has been to give the reader some general idea of ongoing re
search in the area. I have tried to be scientifically accurate but not so
technical that the worker or student from outside the field becomes lost.
The syndromes selected-depression, schizophrenia, anxiety, and alco
holism-are used to illustrate some of the conceptual points made in the
first few chapters. They are all areas of active research investigation, but
of course others could have been included. One is the area of organic
mental disorders. However, the techniques being used are fundamen
tally different from those being used to study the four syndromes dis
cussed and seemed more appropriate as the subject of a separate mono
graph. Another important group of psychiatric disorders are those
involving substance abuse. However, the discussion of animal models
of substance abuse would occupy the full length of this book and more,
since multiple drugs are involved and the techniques for studying the
different drugs vary. The literature is enormous and, in my opinion, also
deserves to be treated in a separate book.
The final section of the book is a synthesis of the key conceptual and
controversial issues in the field of animal modeling. This chapter is
timely because there is great tension between molecularly oriented neu
roscientists and their conceptualization and expectations of animal mod
els, and researchers whose major interest is in the study of ongoing
social behavior. Particularly in this era of high-technology neuroscience,
it is important to remember that behavior occurs in a developmental and
social context and that, if one wants to understand the neurobiological
underpinnings of behavior, existing techniques must be appropriately
adapted and new ones developed to permit the combined study of be
havior and neurobiology.
The author of any book of this scope must be indebted to many
people for making it possible. As mentioned before, Dr. William Bunney
stimulated my interest in this field in 1967. Dr. David Hamburg has been
a continuing source of stimulation and support for my activities in this
area. When I went to the University of Wisconsin in 1969, I had the
opportunity to work closely with Dr. Harry Harlow, who personally
made it possible for me to begin my work at the Wisconsin Primate
Laboratory. Dr. Arthur Prange and Dr. Morris Lipton were my first two
mentors in psychiatric research, and without them I would never have
entered the field in the first place. I have been fortunate to have had very
capable, high quality members in my research group over the years;
with the unpredictability and uncontrollability of research funding in
Preface vii
this controversial area, they deserve special commendation for their
risk-taking.
This book was written while I was a Fellow at the Center for Ad
vanced Studies in Behavioral Sciences at Stanford, California, in 1983-
1984. I acknowledge with great thanks those at the University of
Wisconsin-Madison and at the Center who made this important year
possible. In particular I am grateful for financial support provided by the
John D. and Catherine T. MacArthur Foundation and to Mardi Horowitz
who read and commented on portions of the manuscript.
This book could not have been written without the cooperation and
loving support of my family-Carolyn, Scott, and Julia-to whom this
book is dedicated. They were uprooted from friends and home in
Madison to come to a new place for a year so that I could have the time
to think and to write about an exciting new area of research.
William T. McKinney
Madison, Wisconsin
Contents
Introduction ................................................. 1
I. Fundamental Basis and Justification for a New Comparative
Psychiatry
1. Historical Perspective 7
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Summary of Key Points ................................... 15
References ............................................... 16
2. Philosophical Basis for the Development of Animal Models for
Psychiatric Illnesses ........................................ 19
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
What Are Models? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20
General Kinds of Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . .. 23
Behavioral Similarity Models . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23
Theory-Driven Models .................................. 24
Mechanistic Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25
Empirical Validity Models ............................... 26
The Homology-Analogy Issue ...................... , . . . . .. 27
Why Have Animal Models? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29
Animal Modeling Research in Relationship to Other
Approaches in Psychiatric Research .................... 30
Limitations of Animal Models ............................ " 31
ix
x Contents
Evaluation of Animal Models .............................. 32
Summary of Key Points ................................... 37
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
II. Four Illustrative Case Examples
3. Animal Models for Affective Disorders 43
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 43
History.................................................. 44
Clinical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 47
Pharmacological Models of Depression ..................... 51
Separation Models ........................................ 55
Neurobiological Effects of Maternal Separation ............ 60
Peer Separation Studies ................................. 64
Separation Models: Rationale and Role in Modeling Studies 69
Uncontrollability Models .................................. 71
Chronic Stress Models .................................... 77
Changes in Dominance Hierarchy .......................... 78
Intracranial Self-Stimulation ............................... 78
Conditioned Motionlessness ............................... 79
Behavioral Despair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 79
Animal Models for Mania ................................. 80
Amphetamine-Induced Hyperactivity ................... " 81
Morphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 82
Other Drug-Induced Behaviors ......................... " 82
Non-Drug-Induced Behaviors in Relation to Models of
Mania............................................. 82
6-Hydroxydopamine Models of Mania .................... 83
Summary of Key Points ................................... 85
References ............................................... 86
4. Animal Models for Anxiety Disorders ........................ " 97
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 97
Clinical Context .......................................... 98
Animal Models of Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 104
Operant Conditioning Paradigms ........................ 104
A Model Based on Alteration of Locus Coeruleus Function . 107
A Model Based on Studies of Aplysia ..................... 111
Contents xi
Models Based Primarily on Social Manipulations ........... 114
Phobias and Other Neuroses ............................ 115
General Discussion and Conclusions ....................... 117
Summary of Key Points ................................... 119
References ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 120
5. Animal Models for Schizophrenic Disorders ..................... 125
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 125
The Clinical Syndrome .................................... 127
Clinical Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 129
Criteria for Evaluating Animal Models of Schizophrenia .... 130
Drug-Induced Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 132
Amphetamine and Psychostimulant Models . . . . . . . . . . . . . .. 132
Phenylethylamine Models ............................... 136
Hallucinogen Models ................................... 138
Noradrenergic Reward System Deficit .................... 139
Conditioned-Avoidance-Response Model ................. 139
Arousal Models ........................................ 140
Summary of Key Points ................................... 142
References ...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 144
6. Animal Models for Alcoholism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 147
Introduction .............................................. 147
Genetic Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 151
Techniques Used to Induce Animals to Self-Administer
Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 154
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 154
Electrical Stimulation and Intracerebral Injections .......... 155
Schedule-Induced Polydipsia ............................ 157
Intravenous Self-Administration .......................... 158
Intragastric Self-Administration .......................... 159
Restriction of All Liquid to Ethanol Solutions. . . . . . . . . . . . .. 159
Forced Administration followed by Free Choice ........... 159
Experimental Stressors and Alcohol Intake in Animals ....... 160
Effects of Stressors in Intoxicated Subjects ................ 162
Ethanol Effects in Stressed Subjects ...................... 162
Effect of Stress on the Intake of Alcohol .................. 163
Drugs and Ethanol Intake ................................. 165
Other Variables Influencing Ethanol Intake in Animals .. :.... 166
Alcohol Addiction in Monkeys and Young Chimpanzees ..... 168
Summary of Key Points ................................... 170
References ............................................... 171
xii Contents
III. Perspectives on the Animal Modeling Field
7. Future Tasks .............................................. 179
The Animal Rights Movement ............................. 180
Conceptual Tasks within the Field. . . . . . . . . . . . . . . . . . . . . . . . .. 184
Development of a Basic Science of Animal Modeling ....... 184
Mainstreaming within Psychiatry ......................... 185
Recognition of the Interactive and Multivariate Nature of
Psychopathology ..................................... 187
Recognition of the Limitations of Animal Modeling Research . 189
8. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 191
Index ....................................................... 195