BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE

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The proposed investigation seeks to characterize and distinguish a group of drugs of abuse in terms of their properties as discriminative stimuli. Emphasis will be upon hallucinogens of the indoleamine/phenethylamine type including lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4- methylamphetamine (DOM). All drugs studied behaviorally also will be examined in terms of their binding characteristics at serotonergic and adrenergic receptors. initially, binding will be quantitated at the 5- HT1A. 5-HT1B, 5-HT1C, and 5-HT2 subtypes of the serotonergic receptor and at the alpha and beta adrenergic receptors. Nearly all drugs of abuse are able to assume stimulus control in animals. This fact provides a sensitive and informative approach to the study of the mechanisms of action of a variety of drugs habitually chosen for non- medical use by humans. Complementing discrimination methods, receptor binding techniques provide a unique opportunity to assess the molecular events which underlie specific behavioral effects. Thus, receptor binding and behavioral experiments will be conducted in parallel. The latter will provide evidence either for or against functional significance of a given receptor site. A long-term objective of the proposed research is to achieve an understanding of these complex behavioral effects in biochemical terms and thus to facilitate rational clinical intervention.