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Problems of Drug Dependence, 1985 National Institute on Drug Abuse MONOGRAPH SERIES Problems of Drug Dependence, 1985 Proceedings of the 47th Annual Scientific Meeting The Committee on Problems of Drug Dependence, Inc. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration Problems of Drug Dependence, 1985 Proceedings of the 47th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Editor: Louis S. Harris, Ph.D. NIDA Research Monograph 67 1986 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse Office of Science 5600 Fishers Lane Rockville, Maryland 20857 For sale by the Superintendent of Documents, US. Government Printing Office Washington, DC 20402 NIDA Research Monographs are prepared by the research divisions of the National Institute on Drug Abuse and published by its Office of Science. The primary objective of the series is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, and integra- tive research reviews. Its dual publication emphasis is rapid and targeted dissem- ination to the scientific and professional community. Editorial Advisors Martin W. Adler, Ph.D. Sidney Cohen, M.D. Temple University School of Medicine Los Angeles, California Philadelphia, Pennsylvania Sydney Archer, Ph.D. Mary L. Jacobson Rensselaer Polytechnic Institute National Federation of Parents for Troy, New York Drug-Free Youth Omaha, Nebraska Richard E. Belleville, Ph.D. NB Associates, Health Sciences Rockville, Maryland Reese T. Jones, M.D. Langley Porter Neuropsychiatrlc Institute Karst J. Besteman San Francisco, California Alcohol and Drug Problems Association of North America Washington, D.C. Denise Kandel, Ph.D. College of Physicians and Surgeons of Gilbert J. Botvin, Ph.D. Columbia University Cornell University Medical College New York, New York New York, New York Joseph V Brady, Ph.D. The Johns Hopkins University School of Herbert Kleber, M.D. Medicine Yale University School of Medicine Baltimore, Maryland New Haven, Connecticut Theodore J. Cicero, Ph.D. Washington University School of Richard Russo Medicine New Jersey State Department of Health St. Louis, Missouri Trenton, New Jersey NIDA Research Monograph Series Charles R. Schuster, Ph.D. DIRECTOR, NIDA Jack Durell, M.D. ASSOCIATE DIRECTOR FOR SCIENCE, NIDA EDITOR-IN-CHIEF Parklawn Building, 5600 Fishers Lane, Rockville, Maryland 20857 Foreword The National Institute on Drug Abuse (NIDA) is pleased to publish Problems of Dru De endence 1985, the proceedings of the 47th Annual Scientific meeting of the Committee on Problems of Drug Dependence, Inc. (CPDD). This. meeting was held in Baltimore, Maryland, in June 1985 to commemorate the 50th anniversary of NIDA's intramural research program, the Addiction Research Center (ARC). The ARC is a unique institution seeking to develop a fundamental understanding of drug addiction through multidisciplinary research. The ARC has made significant contributions in basic and clinical pharmacology and the behavioral and neurosciences and continues to provide new insights into the problems of addictive behavior. A symposium entitled "ARC Today" was held in which scientists from the ARC reported their latest findings. Papers from the symposium are included in this monograph. The CPDD is an independent organization of internationally recognized experts in a variety of disciplines related to drug addiction. NIDA and the CPDD share many interests and concerns in developing knowledge that will reduce the destructive effects of abused drugs on the individual and society. The CPDD is unique in bringing together annually at a single scientific meeting an outstanding group of basic and clinical investigators working in the field of drug dependence. This year, as usual, the monograph presents an excellent collection of papers. It also contains progress reports of the abuse liability testing program funded by NIDA and carried out in conjunction with the CPDD. This testing program represents an example of a highly successful government/ private sector cooperative effort. I am sure that members of the scientific community and other interested readers will find this volume to be a valuable "state-of-the-art" summary of the latest research into understanding of the biological, behavioral, and chemical bases of drug abuse. Charles R. Schuster, Ph.D. Director National Institute on Drug Abuse iii The papers in this monograph were presented or read by title at the 47th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, Inc., in Baltimdre, Maryland, June 10-12, 1985. The CPDD, an independent, nonprofit organization, conducts drug testing and evaluations for academic institutions, government, and industry. Louis S. Harris, the editor of the monograph, is chairman of the Department of Pharmacology, Medical College of Virginia, Richmond, Virginia. COPYRIGHT STATUS The figure on page 86 is copyrighted by Intox Press, Inc., and the table on page 5 is copyrighted by Birkhauser Verlag, Basel. They are reprinted by permission; further reproduction of this material without specific permission of the copyright holders is prohibited. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U. S. Government does not endorse or favor any specific commercial product or commodity. Trade or proprietary names appearing in this publication are used only because they are considered essential in the context of the studies reported herein. DHHS publication number (ADM)86-1448 Printed 1986 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of American Statistics Index, Biosciences Information Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Astracts. iv The Committee on Problems of Drug Dependence, Inc. MEMBERS, COMMITTEE ON PROBLEMS OF DRUG DEPENDENCE, INC. Theodore J. Cicero, Chairman Martin W. Adler Thomas F. Burks William L. Dewey Loretta P. Finnegan Marian W. Fischman Roland R. Griffiths Leo E. Hollister Donald R. Jasinski Lloyd D. Johnston John Kaplan Conan Kornetsky Mary Jeanne Kreek William R. Martin Roger E. Meyer Akira E. Takemori EXECUTIVE SECRETARY Joseph Cochin MEMBERS, BOARD OF DIRECTORS Beny J. Primm, Chairman Natl Medical Assn Joseph V. Brady Soc Behavioral Med Raymond W. Houde Am Soc Clini Pharmacol Ther Keith F. Killam Am Soc Pharmacol Exptl Ther Everette L. May Am Chemical Society Jack H. Mendelson Am Psychiatric Assn Lee N. Robins Am Sociological Assn Edward C. Senay Am Medical Assn E. L. Way Am Coll Neuropsychopharmacol James H. Woods Am Psychological Assn v COMMITTEE CHAIRMEN MEMBERS, PROGRAM COMMITTEE Charles W. Gorodetzky By-Laws Louis S. Harris, Chairman Louis S. Harris Everette L. May Scientific Meetings Joyce H. Pye Arthur E. Jacobson Drug Testing Program MEMBERS, COMMITTEE ON ARRANGEMENTS PERMANENT LIAISON Joseph V. Brady Patricia Thiess Harold Kalant Howard McClain Jerome Jaffe Edward C. Tocus CONTRIBUTING FIRMS, 1984-85 The following firms have supported the work of the Committee on Problems of Drug Dependence, Inc. through contributions during the previous fiscal year. Abbott Laboratories Syntex Arthur B. Little Corporation The Upjohn Company Ayerst, Canada Warner Lambert (Park-Davis) Boehringer Ingelheim International Wyeth Laboratories Burroughs Wellcome Company Zambon s.p.a. Ciba-Geigy Corporation Clin-Midy of America, Incorporated DeGussa Corporation Endo Laboratory, Inc. (DuPont) Glaxo Hoffman-La Roche, Inc. ICI Americas, Inc. Imperial Chemicals, Great Britain Johnson & Johnson, Inc. Key Pharmaceuticals, Inc. Knoll Pharmaceutical Company Lilly Research Laboratories McNeil Pharmaceuticals Merck Sharp & Dohme Research Labs Merrell-Dow Pharmaceuticals Miles Laboratories Monsanto Company Ortho Pharmaceutical Corporation Pfizer Central Research Reckitt & Colman Pharmaceutical Div. Sandoz, Ltd. (Basle) Sandot, Inc. (New Jersey) Schering Corporation Searle Research & Development Servier Amerique Smith, Kline & French Laboratories Sterling Drug, Incorporated vi Contents Foreword Charles R. Schuster iii Plenary Session Introduction of Nathan B. Eddy Memorial Award Recipient--1985 William L. Dewey 1 Nathan B. Eddy Memorial Award Lecture Louis S. Harris 4 Introductory Remarks Carlton E. Turner 14 Symposium—ARC Today Studies of Kappa Agonist Karen Kumor, Tsung-Ping Su, Bruce Vaupel, Charles Haertzen, Rolley Ed. Johnson, and Steve Goldberg 18 Metabolic Mapping of the Cerebral Effects of Abused Drugs Edythe D. London, Margit Szikszay, and Mauro Dam 26 Behavioral Pharmacology of Licit Drugs in Experimental Animals Steven R. Goldberg, Jonathan L. Katz, and Marcus E. Risner 36 Pharmacology of Benzodiazepine Antagonists Harlan E. Shannon 45 Human Studies of the Behavioral Pharmacological Determinants of Nicotine Dependence Jack E. Henningfield, Steven R. Goldberg, Ronald I. Herning, Donald R. Jasinski, Scott E. Lukas, Katsumasa Miyasato, Rosemary Nemeth-Coslett, Wallace B. Pickworth, Jed E. Rose, Angela Sampson, and Frederick Snyder
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