MODIFICATION OF ACUTE AND CHRONIC COCAINE EFFECTS

改变急性和慢性可卡因效应

• 批准号: 3874845
• 负责人: WILLIAM L WOOLVERTON
• 金额: --
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874845
• 关键词: Macaca mulatta; central nervous system stimulants; cocaine; discrimination learning; drug abuse chemotherapy; drug addiction; drug addiction antagonist; drug administration rate /duration; drug tolerance; food; inhibitor /antagonist; longitudinal animal study; neuropharmacology; operant conditionings; psychological reinforcement; psychopharmacology; self medication; self stimulation; stimulant /agonist

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.

在美国，可卡因滥用仍然是一个严重的问题。的 项目3中提出的研究旨在调查行为 和可卡因的神经药理学，因为它与可卡因滥用有关。 一系列的研究旨在研究药理学 在猴子身上改变可卡因的强化作用。我们将 研究可卡因与药物的相互作用， 通过拮抗剂或激动剂作用给药。此外，我们将 调查可卡因与其他滥用药物的相互作用。我们 一种假设是，滥用药物的强化作用是 当它们结合在一起时， 第二个系列的目的是检查药理学修改的 可卡因的辨别刺激（DS）效应，一种动物模型， 对人类的主观影响。我们将研究 可卡因与药物，可能会减少其DS效应通过拮抗剂或 激动剂作用此外，我们将研究可卡因的相互作用 其他滥用药物。我们的假设是可卡因的副作用 与其他滥用药物联合使用时会增强药效。 第三个系列将继续我们的行为影响的调查 长期接触可卡因宽容和敏感都有 据报道，当可卡因被反复使用时会出现这种情况。我们 建议调查可卡因的条件的影响 给药（即，连续或间歇性）的发展 对可卡因对操作行为影响的耐受性/敏感性 恒河猴我们还将研究药物敏感性的变化， CNS中的选择性作用（例如，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。 意见。 前两个系列的研究将增加我们对中枢神经系统的认识 参与可卡因刺激作用的行为表明具有治疗作用 可卡因滥用干预措施，并提供对药物滥用的深入了解 组合。第三个系列将增加我们对 长期接触可卡因的影响。其中一个重要方面是 一个提议是我们有能力在一个物种中研究所有这些影响， 恒河猴，并因此直接比较结果，从每一个 三种范式。从这项研究中获得的信息应该 对我们理解人类的行为 可卡因滥用的药理学