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