Behavioral Pharmacology of Human Drug Dependence

Behavioral Pharmacology of Human Drug Dependence U S DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration PROPERTY OF DEPR Behavioral Pharmacology of Human Drug Dependence Editors: Travis Thompson, Ph.D. University of Minnesota Chris E. Johanson, Ph.D. The University of Chicago NIDA Research Monograph 37 July 1981 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National lnstitute on Drug Abuse Division of Research 5600 Fishers Lane Rockville, Maryland 20857 For sale by the sales superintendent of Documents, US Government Printing Office Washington, DC 20402 The NIDA Research Monograph series Is prepared by the Division of Research of the National Institute on Drug Abuse Its primary objective is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, integrative research reviews and significant origInal research Its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community Editorial Advisory Board Avram Goldstein, M.D. Addiciton Research Foundation Palo Alto, California Jerome Jaffe, M.D. College of Physicians and Surgeons Columbia University New York Reese T. Jones, M.D. Langley Porter Neuropsychiatric Institute University of California Son Francisco California Jack Mendelson, M.D. Alcohol and Drug Abuse Research Center Harvard Medical School McLean Hospital Belmont Massachusetts Helen Nowlis, Ph.D. Office of Drug Education DHHS Washington DC Lee Robins, Ph.D. Washington University School of Medicine St Louis Missouri NIDA Research Monograph series William Pollin, M.D. DIRECTOR, NIDA Marvin Snyder, Ph.D. DIRECTOR, DIVISION OF RESEARCH, NIDA Robert C. Petersen, Ph.D. EDITOR-IN-CHIEF Eleanor W. Waldrop MANAGING EDITOR Parklawn Building 5600 Fishers Lone Rockville. Maryland 20857 Behavioral Pharmacology of Human Drug Dependence ACKNOWLEDGMENTS This monograph is based upon papers presented at a technical review held at Belmont Conference Center, Elkridge, Maryland, June 29 to July 1, 1980. Koba Associates, Inc., Washington, D.C., provided administrative support for the meeting under NIDA Con- tract No. 271-79-3607. Drs. Travis Thompson and Chris E. Johanson served on the staff of the Clinical/Behavioral Branch, NIDA Division of Research, during the 1979-1980 academic year by agreement under the Inter- governmental Personnel Act of 1970 (IPA) . Dr. John Grabowski has been serving in a similar capacity since October 1980. Opinions expressed in the papers are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse; Alcohol, Drug Abuse, and Men- tal Health Administration; Public Health Service; or the Depart- ment of Health and Human Services. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this material is prohibited without specific permission of the copyright holders. The table on page 47 is modified from copyrighted material and therefore may be under copyright. It is used with the permission of Silver Burdette Company, Morristown, New Jersey. Before reproducing, readers are advised to determine its copyright status and/or to secure permission of the copyright holder. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or repro- duced without permission from the Institute or the authors. Cita- tion of source is appreciated. Library of Congress catalog card number 81-600105 DHHS publication number (ADM)81-1137 Printed 1981 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of Biosciences Informa- tion Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Abstracts. iv Foreword The behavioral description of drug dependence which began with anecdotal accounts has now progressed to the sophisticated behavioral analysis so well summarized in this monograph. The result of a technical review held by the National Institute on Drug Abuse (NIDA), this book describes a growing body of system- atically derived data on the behavioral mechanisms involved in the use of drugs and their all too frequent abuse. By empha- sizing human use, it provides a valuable link between the neatly arrayed drug use paradigms of the animal laboratory and those governing street drug use. By describing some of the remarkable parallels in many forms of substance abuse--from smoking cigarettes to mainlining heroin--we hope that this monograph will be both a useful con- pendium of what is presently known about the behavioral pharmacology of drug dependence and a spur to additional research. Many difficult issues inherent in this increasingly sophisticated research area have been addressed by an impressive diversity of researchers. As our understanding of these behavioral mechanisms is enhanced, so is the possibility of more effective prevention and treatment. It is that goal-- ultimately minimizing the extent and cost of dysfunctional drug use--to which NIDA dedicates its research efforts. We hope that this book will help to provide the scientifically based foundation upon which better intervention techniques must be built. Robert C. Petersen, Ph.D. Editor-in-Chief NIDA Research Monograph Series v Preface The National Institute on Drug Abuse (NIDA) has published in its Research Monograph series several volumes focusing on the discipline of behavioral pharmacology. These monographs represent only a sampling of the extensive data base which has developed over the past two decades. Their content closely parallels the history of the field, reflecting its foibles as well as its evolution toward greater sophistication. Clearly, many important questions remain, and investigators will not find it difficult to identify areas requiring further research, as is well documented in the pages of this volume. Many investigators have been involved in the expansion of our knowl- edge and understanding of the orderly relationships between drugs and behavior; a few have made particularly notable contributions in the field of drug abuse research. Dr. Joseph Brady, for example, has contributed substantially to the shaping of the discipline itself and to the careers of several of the investigators represented in this volume. Drs. Norman Krasnegor and Pierre Renault, while serving at NIDA, devoted persistent and energetic efforts toward development of an integrated program in behavioral pharmacology of drug dependence. Their work and that of many other individuals has been reflected in this monograph series and in the philosophical and technological evolution of the field. Behavioral pharmacology has evolved into a mature discipline. Drs. Thompson and Johanson have provided us with a monograph indicative of the field's vitality, which both delineates and goes well beyond efforts of the past. Progress in behavioral pharmacology as represented in microcosm in this volume is not a chimera. It is evidenced in two ways. First, "steps beyond" are evident in the hard data. For example, additional important data on aspects of drug self-administration are presented. Drug actions and interactions under a greater variety of circumstances are considered and explicit factors modulating drug effects are more clearly delineated. Specific data based and data bound advances such as these are, and should be, the foundation of science. vii It is from expansion and integration of the data that a second cate- gory of "steps beyond" emanates. In the present volume, the fields and subfields of psychology, psychiatry, pharmacology, and neurology are all represented. Thus it is fair to say that the interdisciplinary nature of behavioral pharmacology is now well established. Rapprochement is clearly increasing. A joining of the conceptual, methodological, and technological approaches of traditional pharma- cological and psychopharmacological perspectives with those of behavioral pharmacology is evident. Each of the disciplines stands to gain from interdisciplinary activity, the sharing of traditional wisdom, and by utilizing innovative techniques--all trends clearly manifested in this monograph. From this vantage point the volume presents an integrated conceptual framework for delineating behavioral mechanisms of drug dependence across a range of levels of analysis. Within the psychological viewpoints represented, the need for recon- ciliation of classical and operant psychological perspectives in analyzing drug use and drug effects has become apparent and has emerged herein. Similarly the need to account for and measure human behavioral idiosyncracies such as verbal behavior, an area in which animal models are limited, is also addressed. It is also evident that better understanding of the limitations of animal models has enhanced their usefulness. As a result data from the animal laboratory has increased our understanding of aspects of drug use and has most certainly disproved Sir William Osler's comment that "the desire to take medicine is perhaps the greatest feature which dis- tinguishes man from animals." Overall, robust and significant link- ages have emerged between basic and applied, and laboratory and clinical, research. The efforts to develop statements concerning

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