ENDOCRINE PHARMACOLOGY OF PSYCHOTROPIC DRUGS

本提案的具体目的是描述 兴奋剂、镇静剂和致幻剂对非 人类灵长类动物模型。虽然我们知道很多关于 几种滥用物质对啮齿动物模型内分泌功能的影响， 特别是鸦片剂和酒精，关于这方面的数据很少。 其他精神药物，如兴奋剂， 抑郁剂和致幻剂，特别是在非人类灵长类动物模型中。 我们的假设是所有可能被滥用的物质 发挥强大的神经内分泌作用，这些变化：首先，可能 允许表征这些化合物，特别是关于 其行为效应和药理学等效性;以及， 第二，可以介导至少一些药理学和 具有重大滥用潜力的物质的生理影响。 此外，我们建议，不同的内分泌概况将是 在具有药物递送的意志控制的动物中观察到， 被动接受药物的人。我们有以下 具体目标。 (l)研究精神科药物的使用方法 药物影响其对内分泌功能的作用。具体而言是 需要解决的问题是，药物的自我给药 产生内分泌的变化， 被动给药观察。一个"上了轭"的非人灵长类动物模型 将用于评估这一重要问题。 (2)为了评估代表性兴奋剂的急性效应， 镇静剂和致幻剂对非人类神经内分泌系统的影响 灵长类动物模型。这些研究将包括评估是否 这些药物引起内分泌功能的变化， 介导的细胞特异性，并与效价相关， 这些药物在行为研究中的疗效评估。 (3)为了确定长期服用这些药物是否会产生 内分泌功能的变化，这些变化与 容忍和退缩的发展和表达。 这些研究的意义在于内分泌功能的变化 可能有助于评估兴奋剂的滥用潜力， 抑郁剂和致幻剂以及它们的后果 虐待激素，因为它们对每个器官都有广泛的影响， 系统中的机构，似乎是理想的候选人调解一些 过量药物摄入的生物医学后果， 作为大脑神经适应性变化的催化剂 这就解释了耐受性和身体依赖性的发展。 使用非人类灵长类动物模型将允许进行严格的评估 这些重要的问题，可能无法解决的任何 其他物种。

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.