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Mechanisms of Tolerance and Dependence, 54 Mechanisms of Tolerance and Dependence U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration Mechanisms of Tolerance and Dependence Editor: Charles Wm. Sharp. Ph.D. Division of Preclinical Research National Institute on Drug Abuse NIDA Research Monograph 54 1984 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, Maryland 20857 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 integrative research reviews. Its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community. Editorial Advisors MARTIN W. ADLER, Ph.D. MARY L. JACOBSON Temple University School of Medicine National Federation of Parents for Philadelphia, Pennsylvania Drug-Free Youth Omaha, Nebraska SYDNEY ARCHER, Ph.D. Rensselaer Polytechnic lnstitute Troy, New York REESE T. JONES, M.D. Langley Porter Neuropsychiatric Institute RICHARD E. BELLEVILLE, Ph.D. San Francisco, California NB Associates, Health Sciences Rockville, Maryland DENISE KANDEL, Ph.D. KARST J. BESTEMAN College of Physcians and Surgeons of Alcohol and Drug Problems Association Columbia University of North America New York, New York Washington, D.C. GILBERT J. BOTVIN, Ph.D. Cornell University Medical College HERBERT KLEBER, M.D. New York. New York Yale University School of Medicine New Haven, Connecticut JOSEPH V. BRADY, Ph. D. The Johns Hopkins University School of Medicine RICHARD RUSSO Baltimore, Maryland New Jersey State Department of Health Trenton. New Jersey THEODORE J. CICERO, Ph. D. Washington University School of Medicine St. Louis, Missouri NIDA Research Monograph Series CHARLES R. SCHUSTER, Ph.D. Director NIDA THEODORE M. PINKERT, M.D., J.D. Acting Associate Director for Science, NIDA Parklawn Building, 5600 Fishers Lane, Rockville, Maryland 20857 Mechanisms of Tolerance and Dependence ACKNOWLEDGEMENT This monograph is based upon papers presented at a technical review which was held on November 11 and 12, 1983, in Boston, Massachusetts. The meeting was sponsored by the Division of Preclinical Research, National Institute on Drug Abuse. 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. 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. 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. Library of Congress catalog card number 84-601105 DHHS publication number (ADM)88-1330 Alcohol, Drug Abuse, and Mental Health Administration Printed 1984 Reprinted 1988 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 Abstracts. iv Contents Preface. ix In Memoriam: H. 0. J. Collier Sydney Archer . 1 Mechanisms of Tolerance and Dependence: An Overview Leo G. Abood . 4 Phenomenology and Theoretical Basis of Tolerance and Dependence William R. Martin. 12 Contributions of Neuropharmacology to Understanding Mechanisms of Tolerance and Dependence Martin W. Adler and Ellen B. Geller. 27 Various Factors Which Affect the Rate of Development of Tolerance and Physical Dependence to Abused Drugs William L. Dewey . 39 Genetic Determinants of Responses to Drugs of Abuse: An Evaluation of Research Strategies Louis Shuster . 50 Opioid Tolerance and Dependence in Light of the Multiplicity of Opioid Receptors Rudiger Schulz and Albert Herz . 70 Sites and Mechanisms of Dependence in the Myenteric Plexus of Guinea Pig Ileum H. 0. J. Collier and J. F. Tucker . 81 Biochemical Reactions Between Opiate Receptor Binding and Inhibition of Neurotransmission Doris H. Clouet and Norifumi Yonehara . 95 The Role of Adenyl Cyclase in Opiate Tolerance and Dependence Werner A. Klee, Graeme Milligan, William S. Simonds, and Bruno Tocque . 109 v Mechanisms of Multiple Cellular Adaptation Processes in Clonal Cell Lines During Chronic Opiate Treatment Ping-Yee Law, Michael T. Griffin, and Horace H. Loh . 119 The Opioid-Induced Desensitization (Tolerance) in Neuroblastoma X Glioma NG 108-15 Hybrid Cells: Results from Receptor Uncoupling Michael Wuster and Tomnaso Costa . 136 Opiate Receptor Upregulation and Functional Supersensitivity R. Suzanne Zukin, Ann Tempel, and Eliot L. Gardner. 146 The Role of Dynorphin in Narcotic Tolerance Mechanisms Nancy M. Lee . , . 162 Post-Translational Processing of Neuropeptide Precursors Richard E. Mains and Betty A. Eipper . 168 Opiate-Mediated Control of Luteinizing Hormone in the Male; Role in the Development of Narcotic Tolerance and Physical Dependence Theodore J. Cicero . 184 Modulation of Opioid Physical Dependence During the Hibernation Cycle Alexander L. Beckman, Carmen Llados-Eckman, Steven K. Salzman, and Toni L. Stanton . 209 Neurophysiological Investigations of Opiate Tolerance and Dependence in the Central Nervous System Steven Jon Henriksen . 239 Spinal Cord Tissue Culture Models for Analyses of Opioid Analgesia, Tolerance and Plasticity Stanley M. Crain . 260 Experimental Approaches Toward Determining the Neuronal Circuits Most Affected by Chronic Opiate Administration Robert Elde . 293 Effects of Opiates and Neuropeptides on Immune Functions Robert E. Faith, N. P. Plotnikoff, and A. J. Murgo. 300 Changes in CNS Sensitivity to Cannabinoids with Repeated Treatment: Tolerance and Auxoesthesia R. Karler, L. D. Calder, and S. A. Turkanis . 312 Catecholamine-Independent Behavioral and Neurochemical Effects of Cocaine in Rats Karen Gale . 323 Barbiturate Tolerance and Physical Dependence: Contribution of Pharmacological Factors Michiko Okamoto . , . 333 vi Behavioral and Biochemical Studies in Rats After Chronic Exposure to Nicotine Leo G. Abood, Susan Grassi, Maria Costanzo, and Jeffrey Junig . 348 Psychobiological Foundations of Behaviors Induced by Amphetamines Philip M. Groves and David S. Segal . 356 Index . 367 List of NIDA Research Monographs . 371 vii Preface When the topic of mechanisms of tolerance/dependence was considered by the National Institute on Drug Abuse for a major review, it seemed at first to lack sufficient substance. Although there is voluminous material on pharmacological dose response and on signs and symptoms associated with the actions of opiates and other drugs, only limited progress has been made on defining the basic mechanisms involved. For several reasons, progress has been slow in this area. As Eric Simon stated at the symposium, progress has been encumbered by several factors, some of which will eventually assist in defining basic biochemical systems and subsequently the area of tolerance and dependence. These include the discovery that there are several types of opiate receptors, the discovery of at least three types of endogenous pro-opioid peptides, the difficulties in measuring dynamic biological turnover of these peptides and/or related systems; the lack of an understanding of post-receptor events (especially in vivo); and finally, the difficulty in establishing any regulation of opiate receptors. Yet progress has been made, and it is essential that we continue to define the mechanisms of tolerance and/or dependence. This knowledge is important in determining the underlying biological factors that lead some individuals to abuse drugs. When we have more precise knowledge of these processes we will be able to cope more effectively with the ever increasing drug problem. It took the quiet enthusiasm of Professor H.O.J. Collier during a visit to NIDA in late 1982 to instigate this review. His confidence in his colleagues and especially in his own work was contagious. Once the seed had been planted with Institute Director Dr. William Pollin and the rest of the NIDA staff, we undertook the task of organizing this review of important recent findings defining the mechanisms of tolerance and dependence. We were buoyed by the interest and enthusiasm of those we spoke with regarding a discussion of this topic--one that has been of major concern to NIDA for a long time. Ever since the discovery of endogenous opioids in 1975, the Institute has encouraged investigators not only to identify the site of action of those substances, but more importantly, to utilize these substances and their systems to study the mechanisms through which tolerance and/or dependence are mediated. ix Unfortunately, shortly before the meeting, Professor Collier died. Thus, not only did the group miss his knowledgeable contributions, we missed and will continue to miss his probing and articulate discussions. In lieu of the original thoughts Professor Collier would have contributed at the meeting, it is worth reflecting
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