MODIFICATION OF ACUTE AND CHRONIC COCAINE EFFECTS

可卡因滥用在美国仍然是一个严重的问题。 项目3中提出的研究旨在调查 可卡因的神经药理学，因为它与可卡因滥用有关。 一系列研究旨在调查药理学 可卡因对猴子增强作用的修饰。我们会 研究可卡因与可能降低自身免疫力的药物之间的相互作用 通过拮抗剂或激动剂的作用给药。此外，我们还将 调查可卡因与其他滥用药物的相互作用。我们的 假说是滥用药物的强化作用是 当它们结合在一起时就会增强。 第二个系列的设计是为了研究药物修饰 可卡因的辨别性刺激效应 它们对人类的主观影响。我们将研究以下因素的相互作用 可卡因与可能通过拮抗剂或药物降低DS效应的药物 激动剂作用。此外，我们还将研究可卡因的相互作用 与其他滥用药物有关。我们的假设是可卡因的DS效应 与其他滥用药物结合使用时会得到加强。 第三系列将继续我们对行为影响的调查 长期接触可卡因。耐受性和敏感度都有 据报道，当反复服用可卡因时会发生这种情况。我们 建议调查可卡因条件的影响 给药(即，连续或间歇性) 对可卡因对操作者行为影响的耐受/敏化 恒河猴。我们还将检查药物敏感性的变化 中枢选择性作用(如多巴胺激动剂)收集 与中枢神经系统变化相关的信息可能是我们行为的基础 观察。 前两个系列的研究将增加我们对中枢神经系统的了解 与可卡因的刺激作用有关的行为，暗示有治疗作用 对可卡因滥用的干预措施和对药物滥用的洞察 组合。第三个系列将增加我们对 长期接触可卡因的影响。这其中的一个重要方面 建议是我们有能力在单个物种中研究所有这些影响， 恒河猴，因此直接比较每一种的结果 三种范式。从这项研究中获得的信息应该 对我们理解行为有重大贡献 可卡因滥用的药理学。

Cocaine abuse continues to be a significant problem in the U S. The research proposed in Project 3 is designed to investigate the behavioral and neuropharmacology of cocaine as it relates to cocaine abuse. One series of studies is designed to investigate pharmacological modification of the reinforcing effects of cocaine in monkeys. We will examine the interaction of cocaine with drugs that may reduce its self-- administration via an antagonist or an agonist action. In addition, we will investigate the interaction of cocaine with other drugs of abuse. Our hypothesis is that the reinforcing effects of drugs of abuse are potentiated when they are combined. The second series is designed to examine pharmacological modification of the discriminative stimulus (DS) effects of cocaine, an animal model of their subjective effects in humans. We will examine the interaction of cocaine with drugs that may reduce it's DS effect via an antagonist or an agonist action. In addition, we will examine the interaction of cocaine with other drugs of abuse. Our hypothesis is that the DS effects of cocaine are potentiated in combination with other drugs of abuse. The third series will continue our investigation of the behavioral effects of prolonged exposure to cocaine. Both tolerance and sensitization have been reported to develop when cocaine is administered repeatedly. We propose to investigate the influence of conditions of cocaine administration (i.e., continuous or intermittent) on the development of tolerance/sensitization to the effects of cocaine on operant behavior in rhesus monkeys. We will also examine changes in sensitivity to drugs with selective actions in the CNS (e.g., dopamine agonists) to collect information relevant to the CNS changes that may underlie our behavioral observations. The research in the first 2 series will increase our knowledge of the CNS actions involved in the stimulus effects of cocaine, suggest therapeutic interventions for cocaine abuse and provide insights into the abuse of drug combinations. The third series will increase our understanding of the effects of longterm exposure to cocaine. An important aspect of this proposal is our ability to study all of these effects in a single species, the rhesus monkey, and therefore to directly compare results from each of the 3 paradigms. The information gained from this research should contribute significantly to our understanding of the behavioral pharmacology of cocaine abuse.