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Drug Discrimination: Applications to Drug Abuse Research

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Drug Discrimination: Applications to Drug Abuse Research National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Drug Discrimination: Applications to Drug Abuse Research 116 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Drug Discrimination: Applications to Drug Abuse Research Editors: Richard A. Glennon, Ph.D. Medical College of Virginia Virginia Commonwealth University Torbjörn U.C. Järbe, Ph.D. Department of Psychology University of Uppsala Jerry Frankenheim, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Research Monograph 116 1991 U.S. 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, MD 20857 ACKNOWLEDGMENT This monograph is based on the papers from the “International Drug Discrimination Symposium” held from June 25 to June 27, 1990, in Noordwijkerhout, The Netherlands. 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 copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. 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 US. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this publication are used only because they are considered essential in the context of the studies reported herein. 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. DHHS publication number (ADM)92-1878 Printed 1991 ii Contents Introduction . .1 Richard A. Glennon A Historical Perspective on Drug Discrimination . .5 Donald A. Overton Discriminative Stimulus Properties of Hallucinogens and Related Designer Drugs . 25 Richard A. Glennon Discriminative Stimulus Properties of Amphetamine, Cathinone, and Related Agents . 45 A.J. Goudie Discriminative Stimulus Effects of Cocaine . .61 William L. Woolverton Discriminative Stimulus Functions of Cannabinoids/Cannabimimetics . .75 Torbjörn U.C. Järbe and Diane A. Mathis Discriminative Stimulus Properties of Nicotine: Mechanisms of Transduction . .101 John A. Rosecrans and Heidi F. Villanueva Discriminative Stimulus Properties of Benzodiazepines and Several New Anxiolytics . 117 Richard Young iii Distinctive Discriminative Effects of Ethanol . 131 Herbert Barry III Training Dose: Influences in Opioid Drug Discrimination . 145 Sandra D. Comer, Charles P. France, and James H. Woods Discriminative Stimulus Properties of Phencyclidine and Other NMDA Antagonists . 163 Robert L. Balster Discriminative Stimulus Effects of Psychomotor Stimulants and Benzodiazepines in Humans . 181 Chris-Ellyn Johanson Tolerance to Drugs Acting as Discriminative Stimuli . 197 Alice M. Young Tolerance: Role of Conditioning Processes . 213 Shepard Siegel Responding to Drug-Related Stimuli in Humans as a Function of Drug-Use History . 231 Ronald N. Ehrman, Steven J. Robbins, Anna Rose Childress, A. Thomas McLellan. and Charles P. O’Brien State Dependency as a Mechanism of Central Nervous System Drug Action . 245 Francis C. Colpaert State-Dependent Learning With Social Drugs . 267 Geoff Lowe Discriminative Stimulus Effects of Drug Mixtures in Rats . 277 I.P. Stolerman, E.A. Mariathasan, and H. S. Garcha iv Application of Drug Discrimination With Drugs of Abuse To Develop New Therapeutic Agents . 307 Theo Frans Meert Intracranial Stimulation as Reinforcer for Neuropeptide Discrimination . 325 Muriel Gewiss, Christian Heidbreder, and Philippe De Witte Drug Discrimination Used To Study Drug Withdrawal . 337 M. W. Emmett-Oglesby and G.A. Rowan Schedule-Induced Self-Injection of Drugs . 359 George Singer Use of Drug Discrimination in Drug Abuse Research . 369 James B. Appel, Lisa E. Baker, Rita L. Barrett, Julie Broadbent, Elizabeth M. Michael, Elizabeth E. Riddle, and Bette J. Van Groll Symposium Critique . 399 L.S. Harris v For sale by the U.S. Government Printing Office Superintendent of Documents, Mail Stop: SSOP, Washington, DC 20402-9328 ISBN 0-16-036035-8 Introduction Richard A. Glennon The drug discrimination (DD) paradigm is essentially a drug detection procedure whereby animals are trained to recognize or discriminate the stimulus effects of a given dose of a particular training drug from those of (1) a different dose of the same training drug, (2) a different training drug, or, more commonly, (3) saline/vehicle (i.e., a nondrug condition). The most commonly employed apparatus for conducting drug discrimination studies is a two-lever operant chamber; however, several other types of test procedures, including three-lever chambers, are also being used. Several species of animals are quite popular, primarily rat, pigeon, and monkey; the use of other species, including human, is now becoming more common. The DD paradigm, by itself, cannot be used to completely characterize a novel agent. This is true of any pharmacological procedure. However, the DD paradigm can be used to investigate a wide variety of pharmacological aspects relating to the stimulus properties of a drug. These aspects include, for example, time of onset and duration of action, mechanism of action, similarity of effect to other agents, structure-activity relationships, activity of metabolites, and identification and development of potential antagonists. Recently, the paradigm has been used to investigate the processes of tolerance and withdrawal. There have already been several international drug discrimination symposia. For the most part, these symposia were concerned more with the technique itself than with the application of the technique for the investigation of a particular problem. Prior emphasis has been on, for example, the use of drug discrimination in central nervous system pharmacology and on the transduction mechanisms involved in the stimulus effects of drugs. Because many of the drugs used in DD studies have a potential for abuse or, indeed, are already noted for their abuse, we felt the time was right to address the application of DD in drug abuse research. 1 This monograph presents selected papers from the 1990 International Drug Discrimination Symposium held in Noordwijkerhout, The Netherlands, June 25-27,1990. The symposium was cosponsored by the European Behavioral Pharmacology Society and the Society for the Stimulus Properties of Drugs. The theme for the 1990 symposium was “Drug Discrimination: Applications in Drug Abuse Research.” The meeting consisted of a number of invited presentations on drug abuse research; it was also open to a general poster session. Abstracts for most of the presentations were published as a supplement to Psychopharmacology volume 101,1990. Unlike previous symposia, this meeting brought together members of the international academic, industrial, government, and drug enforcement communities to discuss the relevance and application of the paradigm to a single health-related issue: drug abuse. Presentations ranged from the basic science, such as mechanisms of action and structure-activity relationships, to DD studies involving human subjects, to the role of DD in the legal control of abused substances. Another topic of interest was the use of abused substances as training drugs for developing new therapeutic agents. The consensus of the symposium participants was that the DD paradigm is an important, useful, and very versatile tool for investigating drugs of abuse. However, the committee invited several speakers to address this issue in a formal sense. A separate session devoted to this topic was entitled “Invited Perspectives.” The committee selected a member of the U.S. Drug Enforcement Administration (Dr. F. Sapienza) to address the issue from a law enforcement perspective. Two additional speakers were also requested to critique the DD paradigm and/or the symposium per se. To obtain a balanced viewpoint, one speaker (Dr. J. Appel) was selected because of his contributions to the field of DD research and because he could address the issues as an informed insider. The other speaker (Dr. L. Harris) has had extensive experience in the field of drug abuse research and is familiar with the technique of DD but does not actively conduct such studies in his own laboratory; his comments may be taken as those of an unbiased outsider. Dr. Harris was given the difficult task of critiquing the entire symposium. The Scientific Organizing Committee for the symposium was composed of Dr. Richard A. Glennon (United States, chair), Dr. Toby Järbe (Sweden, cochair), Dr. John A. Rosecrans (United States), Dr. Ian P. Stolerman (United Kingdom), and Dr. Alice M. Young (United States). The Scientific Organizing Committee was assisted by a local organizing committee without whose help the symposium would have been impossible. The
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