Handbook of Psychopharmacology: Volume 7: Principles of Behavioral Pharmacology

460 Pages·1977·3.5 MB·English

by  J. H. Mackintosh, M. R. A. Chance, A. P. Silverman (auth.), Leslie L. Iversen, Susan D. Iversen, Solomon H. Snyder (eds.)

Handbook of
Psychopharmacology
Volume 7
Principles of Behavioral Pharmacology
Handbook of
Psychopharmacology
SECTION I: BASIC NEUROPHARMACOLOGY
Volume 1 Biochemical Principles and Techniques in Neuropharmacology
Volume 2 Principles of Receptor Research
Volume 3 Biochemistry of Biogenic Amines
Volume 4 Amino Acid Neurotransmitters
Volume 5 Synaptic Modulators
Volume 6 Biogenic Amine Receptors
SECTION II: BEHAVIORAL PHARMACOLOGY IN ANIMALS
Volume 7 Principles of Behavioral Pharmacology
Volume 8 Drugs, Neurotransmitters, and Behavior
Volume 9 Chemical Pathways in the Brain
SECTION III: HUMAN PSYCHOPHARMACOLOGY
Volume 10 N euro leptics and Schizophrenia
Volume 11 Stimulants
Volume 12 Drugs of Abuse
Volume 13 Biology of Drug Effects in Affective Disorders
Volume 14 Anxiety and Affective Disorders: Drug Actions in Man
Volume 7
Principles of Behavioral Pharmacology
Edited by
Leslie L. Iversen
Department of Pharmacology
University of Cambridge
Susan D. Iversen
Department of Psychology
University of Cambridge
and
Solomon H. Snyder
Departments of Pharmacology and Psychiatry
The Johns Hopkins University
School of Medicine
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Handbook of psychopharmacology.
Includes bibliographies and indexes.
CONTENTS: v. 1. Biochemical principles and techniques in neuropharmacology.
-v. 2. Principles of receptor research.-v. 3. Biochemistry of biogenic amines.-v. 4.
Amino acid neurotransmitters.-v. 5. Synaptic modulators.-v. 6. Biogenic amine
receptors.-v. 7. Principles of behavioral pharmacology. 1. Psychopharmacology.
I. Iversen, Leslie Lars. II. Iversen, Susan D., 1940- III. Snyder, Solomon H.,
1938- [DNLM: 1. Psychopharmacology. QV77 H236j
RC483.H36 615.78 75-6851
lSBN-13: 978-1-4613-4216-8 e-lSBN-13: 978-1-4613-4214-4
DOl: 10.1007/978-1-4613-4214-4
© 1977 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1977
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
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 pennission from the Publisher
CONTRIBUTORS
TO VOLUME 7
P. L. BROADHURST, Department oj Psychology, University oj Birmingham, Birming-
ham, England
BYRON A. CAMPBELL, Department oj Psychology, Princeton University, Princeton,
New Jersey
M. R. A. CHANCE, Sub-Department oj Ethology, University oj Birmingham,
Birmingham, England
P. B. DEWS, Laboratory oj Psychobiology, Department oj Psychiatry, Harvard
Medical School, Boston, Massachusetts
Jo DEWEESE, Laboratory oj Psychobiology, Department of Psychiatry, Harvard
Medical School, Boston, Massachusetts
R. T. KELLEHER, Haroard Medical School, New England Regional Primate
Research Center, S01Jihborough, Massachusetts
R. KUMAR, Institute oj Psychiatry, De Crespigny Park, London, England
PAUL D. MABRY, Department oj Psychology, Princeton University, Princeton, New
Jersey
J. H. MACKINTOSH, Sub-Department oj Ethology, University oj Birmingham,
Birmingham, England
JOHN F. MARSHALL, The Psychobiology Program, Departmer/Js oj Psychology and
Psychiatry, University oj Pittsburgh, Pittsburgh, Pennsylvania
J. W. McKEARNEY, Worcester FourukJJion for Experimental Biology, Shrewsbury,
Massachusetts
PETER M. MILNER, Department oj Psychology, McGiU University, Montreal, Quebec,
Canada
W. H. MORSE, Laboratory oj Psychobiology, Haroard Medical School, Boston,
Massachusetts
STATA NORTON, Department oj Pharmacology and Ralph L. Smith Mental
Retardation Research Center, University oj Kansas Medical Center, Kansas City,
Kansas
T. W. ROBBINS, Psychological Laboratory, University oj Cambridge, Cambridge,
England
v
vi
CONTRIBUTORS TO VOLUME 7
A. P. SILVERMAN, Central Toxicology Laboratory, Imperini Chemical Industries Ltd.,
Alderley Park, Cheshire, England
1. P. STOLERMAN, MRC Neuropharmacology Unit, The Medical School, Birming-
ham, England
PHILIP TEITELBAUM, Department of Psychology, University oj Illinois, Champaign,
Illinois
LUIGI V ALZELLI, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy
PREFACE
The first six volumes of the Handbook reviewed basic neuropharmacology,
drawing on expertise in biochemistry, pharmacology and electrophysiology.
The next three volumes focus attention on the functional importance of
these basic neuropharmacological mechanisms for normal behavior.
In order to study this interface in the intact functioning organism,
appropriate methods for describing and quantifying behavior must be
developed. The past twenty years have witnessed a revolution in the study of
behavior which has taken us away from the often fruitless theoretical
arguments to descriptive behaviorism. Technical achievements in the design
of apparatus and the recording of behavior played an important role in these
developments, and the resultant behavioral methods have been accepted and
found useful in studying the effects of drugs. The development of psycho-
pharmacology as a discipline owes as much to these behavioral methods as it
does to the basic neuropharmacological techniques pioneered for in vitro
studies.
In the first section of Volume 7, an effort has been made to provide
reviews both of theory and practice in behavioral science. Milner's chapter
deals with the concept of motivation in a theoretical framework. By contrast,
the chapters by Morse et al. and Dews and DeWeese provide a more
descriptive view of the various ways in which aversive stimuli control behavior
and the importance of schedules of reinforcement in determining the profile
of responding in the animal. The equal importance of observational behav-
ioral methods is well illustrated by Mackintosh et al., and a more detailed
treatment of the analysis of sequences of behavior is provided by Norton.
Other contributors illustrate how a variety of these behavioral approaches
and methods may be combined in the analysis of a particular problem.
Marshall and Teitelbaum do this admirably for motivation, and Kumar
discusses the progress that has been made in developing animal models of
certain human behavioral disorders.
In the remaining section of Volume 7, attention is paid to the general
factors that determine the proftle of behavioral responses in the individual
and their potential for modification by drugs. This represents an immensely
VII
viii PREFACE
important and growing area in psychopharmacology. Genetic factors, devel-
opmental experience, social experience, and drug experience have been
selected for review.
Global descriptions of behavior often seem far removed from the
detailed workings of brain neuropharmacology. In Volume 8 this chasm is
bridged. In some areas we are beginning to understand how function at the
neuronal level is related to overt behavior. This is so in the case of eating,
drinking, sex, sleep, and memory, and the volume provides reviews in these
areas.
Certain areas, however, remain highly controversial, and it was consid-
ered important to represent the unresolved as well as the resolved issues.
The neural and neuropharmacological basis of reinforcement is one such
problem, and Routtenberg and Stein et ai. provide provocative reviews from
two points of view. An effort has also been made to include reference to
more diffuse areas of behavioral control such as behavioral inhibition.
Warburton and Gray review this topic from different theoretical positions
and illustrate how difficult it is to devise specific behavioral tests for certain
nervous functions. Yet it may be that these more global levels of control al e
of immense importance in behavioral integration.
Finally, in Volume 9 the structural basis of neuropharmacology is
considered. Are neuropharmacological systems, for example, a particular
class of receptor or neurotransmitter, localized in the brain? And if so, how
do we go about unraveling the details of this organization? Histochemical
techniques for localizing acetylcholine, catecholamine, and indoleamine path-
ways in the brain are reviewed and information presented on our current
knowledge of the anatomical distribution of these transmitter pathways in the
central nervous system. Alternative methods using radioautography and
immunofluorescence are also considered. These techniques are already
proving to be of immense importance in studying neurotransmitter localiza-
tion at the neuronal level and, in particular, in the study of novel neuromo-
dulators such as the peptides, where conventional histochemical methods are
not available. Lesion techniques have traditionally played an important role
in unraveling neural organization and continue to do so in conjunction with
the specific histological techniques. The problems associated with lesion
techniques are also considered. This volume is a fair reflection of the current
state of knowledge regarding the anatomical basis of neuropharmacology
and is invaluable to those seeking to understand the basis of behavior and its
modification of psychotropic drugs.
L.L.1.
S.D. I.
S.H.S.
CONTENTS
METHODS FOR STUDYING UNCONDITIONED AND
CONDITIONED BEHAVIOR
CHAPTER 1
The Contribution of Ethological Techniques to the Study of Drug Effects
J. H. MACKINTOSH, M. R. A. CHANCE, and A. P. SILVERMAN
1. Introduction ....................................... 3
2. Behavior of Laboratory Rodents ...................... 5
2.1. Exploration .................................... 6
2.2. Eating and Drinking ............................ 6
2.3. Digging and Nest-Building ....................... 7
2.4. Social Behavior ................................. 7
2.5. Analysis of Behavior ............................ 10
2.6. Social Structure ................................ 15
3. Pharmacological Investigations ........................ 17
3.1. Chlorpromazine ................................ 17
3.2. Ethyl Alcohol .................................. 18
3.3. Nicotine ....................................... 20
3.4. Trichloroethylene Vapor ........................ 22
3.5. Cannabis ...................................... 22
4. Effect of Olfactory Signals on Behavior ................ 25
5. Ethological Methods in Clinical Drug Trials ............ 28
6. Discussion .......................................... 29
7. References ......................................... 31
ix
x CONTENTS
CHAPTER 2
A Critique of the Methods Available for the Measurement of Spontaneous
Motor Activity
T. W. ROBBINS
1. Introduction ....................................... 37
2. Methods of Measuring Locomotor Activity ............. 38
2.1. Photocell Cages ................................. 39
2.2. Running Wheels. . .. . . . .. . . . . . . . . . . ..... . . . . . . . . 40
2.3. Stabilimeters and Jiggle Cages .................... 40
2.4. Tilt Cages ..................................... 41
2.5. Open Fields .................................... 41
2.6. Direct Observation .............................. 43
3. Internal and External Factors That Affect Activity ...... 47
3.1. Baseline Levels of Activity ....................... 48
3.2. Internal Factors ................................ 50
3.3. External Factors ................................ 55
4. Statistical Analysis of Results .......................... 57
4.1. Locomotor Activity ............................. 57
4.2. Rating Scales ................................... 58
5. Combining Modes of Measurement ................... 63
6. Exploration and Its Measurement ..................... 64
6.1. Introduction ................................... 64
6.2. Methodological Considerations ................... 65
6.3. Conclusions .................................... 75
7. References ......................................... 77
CHAPTER 3
The Study of Sequences of Motor Behavior
STATA NORTON
1. Introduction ....................................... 83
2. The Organization of Behavior ........................ 85
2.1. Sequences of Behavior (Behavior Patterns) ......... 87
2.2. Interval Histograms of Acts ...................... 93
2.3. Duration of Acts ................................ 94
2.4. Frequency of Acts .............................. 96
2.5. The Motor Act ................................. 97
2.6. Conclusions .................................... 98
3. Methods of Analysis ................................. 99
3.1. Environmental Factors .......................... 99
3.2. Data-Recording................................. 100
3.3. Reliability of Observers .......................... 101