ENDOCRINE PHARMACOLOGY OF PSYCHOTROPIC DRUGS

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The specific aims of this proposal are to characterize the effects of stimulants, depressants and hallucinogens on endocrine function in non- human primate models. Although we know a good deal about the effects of several abused substances on endocrine function in rodent models, notably opiates and alcohol, there is a paucity of data regarding the endocrine effects of other psychotropic drugs, such as the stimulants, depressants and hallucinogens particularly in non-human primate models. Our working hypothesis is that all substances with abuse potential exert potent neuroendocrine effects and that these changes: first, may permit a characterization of these compounds, particularly with respect to their behavioral effects and pharmacological equivalency; and, second, may mediate at least some of the pharmacological and physiological effects of substances with significant abuse potential. Furthermore, we propose that different endocrine profiles will be observed in animals with volitional control of drug delivery as opposed to those who receive the drugs passively. We have the following specific aims. (l) To examine whether the method of administration of psychotropic drugs influences their effects on endocrine function. Specifically, the question to be addressed is whether the self-administration of drugs produces changes in endocrine profiles which are similar to those observed with passive administration. A "yoked" non-human primate model will be used to assess this important issue. (2) To assess the acute effects of representative stimulants, depressants and hallucinogens on neuroendocrine systems in non-human primate models. These studies will include an assessment of whether these drugs produce changes in endocrine function which are receptor- mediated pharmacologically specific and correlate with potency or efficacy estimates of these drugs in behavioral studies. (3) To determine whether chronic administration of these drugs produces changes in endocrine function which correlate systematically with the development and expression of tolerance and withdrawal. The significance of these studies is that changes in endocrine function may be useful in assessing both the abuse potential of stimulants, depressants and hallucinogens as well as the consequences of their abuse. Hormones, because of their pervasive effects on every organ system in the body, would seem to be ideal candidates to mediate some of the biomedical consequences of excessive drug-intake and could also serve as a catalyst for the neuroadaptive changes occurring in brain which account for the development of tolerance and physical dependence. The use of non-human primate models will permit a rigorous assessment of these important problems which probably cannot be addressed in any other species.