ENDOCRINE PHARMACOLOGY OF PSYCHOTROPIC DRUGS

这项提案的具体目的是描述 兴奋剂、镇静剂和致幻剂对非精神分裂症患者内分泌功能的影响 人类灵长类动物模型。尽管我们对其影响了解很多 在啮齿动物模型中，几种滥用物质对内分泌功能的影响， 值得注意的是，关于阿片剂和酒精的数据很少 其他精神药物的内分泌作用，如兴奋剂， 镇静剂和迷幻剂，特别是在非人类灵长类动物模型中。 我们的工作假设是所有有滥用潜力的物质 产生强大的神经内分泌效应，这些变化：第一，可能 允许对这些化合物进行表征，特别是在尊重 它们的行为效应和药理等效性；以及， 第二，可能至少在一定程度上调节药理和 具有显著滥用潜力的物质的生理效应。 此外，我们建议不同的内分泌特征将是 在有意愿控制药物输送的动物中观察到的相反 给那些被动接受药物的人。我们有以下几个方面 明确的目标。 (L)审查精神药物的给药方法 药物影响内分泌功能。具体地说， 需要解决的问题是，药物的自我给药 在内分泌方面产生变化，类似于 被动给药观察。一种“带轭”的非人类灵长类动物模型 将被用来评估这一重要问题。 (2)评估具有代表性的兴奋剂的急性影响， 镇静剂和迷幻剂对非人类神经内分泌系统的影响 灵长类模型。这些研究将包括评估是否 这些药物会引起内分泌功能的变化，内分泌功能是受体- 介导的药理学特异性，并与效力或 这些药物在行为学研究中的疗效评估。 (3)确定长期服用这些药物是否会产生 内分泌功能的变化，这与系统相关 宽容与退缩的发展与表达。 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， 镇静剂和迷幻剂以及它们的后果 虐待。荷尔蒙，因为它们对每个器官都有普遍的影响 在身体系统中，似乎是理想的候选人来调解一些 过量吸食药物的生物医学后果，还可能 是大脑中发生的神经适应性变化的催化剂 这解释了耐受性和身体依赖的发展。 使用非人类灵长类动物模型将允许进行严格的评估 在这些重要的问题中，可能无法在任何 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.