PHARMACOTHERAPIES OF COCAINE ADDICTION IN RATS

大鼠可卡因成瘾的药物治疗

• 批准号: 7459048
• 负责人: Therese A Kosten
• 金额: $ 10.84万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459048
• 关键词: Animals; Behavioral; Binding; Cocaine; Cocaine Dependence; Cues; Data; Discipline; Disruption; Dose; Extinction (Psychology); Human; Intravenous; Laboratories; Lead; Maintenance; Modeling; Outcome; Pharmaceutical Preparations; Pharmacotherapy; Primates; Principal Investigator; Procedures; Property; RNA; Rate; Rattus; Relapse; Running; Self Administration; Series; Site; Testing; Writing; analog; base; dopamine transporter; experience; novel; response

Project 3 is one in the series of well-coordinated studies representing multiple disciplines aimed at evaluating potential pharmacotherapies for cocaine addiction and written in response to SPIRCAP RNA DA 00-001. This series of studies will examine novel 3-phenyltropane analogs of cocaine developed by the Principal Investigator, Dr. F. Ivy Carroll. These compounds posses properties suggestive of pharmacotherapeutic value; they bind potently and selectively to the dopamine transporter, a well- recognized site involved in the behavioral effects of cocaine, and have a slow-onset and long-duration of action, attributes believed to be necessary for effective medications for cocaine addiction. Project 3 will examine the effects of a set of these compounds on intravenous cocaine self- administration in rats and provide information for the primate self- administration studies (Project 4). Our laboratory is experienced in this procedure and is currently running such studies. The first aim of Project 3 is to evaluate six compounds (two doses each) selected for their ability to generalize to the cocaine discriminative cue with minimal disruption of response rates (results obtained from Project 2). We will examine whether these compounds alter maintenance of cocaine self-administration. Results will lead to selection of four compounds to be tested in Project 4. Compounds selected would provide a downward shift in the cocaine dose response function as this is the best indicator of an effective pharmacotherapeutic agent for cocaine addiction based on self- administration data obtained in animals. The second aim of Project 3 is to examine two compounds for their effects on cocaine-induced reinstatement of responding after extinction of lever-press responding for cocaine. This procedure, a well-establishment model of "relapse", is set- up and running in our laboratory. The specific outcomes of aim 2 of Project 3 are to determine whether the compound block-induced reinstatement or cause reinstatement. Data obtained from this aim will be used, in conjunction with results from Projects 2 and 4, to inform the decision to proceed with studies in humans. (Projects 5 and 6).

项目 3 是代表多个学科的一系列协调良好的研究之一，旨在评估可卡因成瘾的潜在药物疗法，并根据 SPIRCAP RNA DA 00-001 编写。这一系列研究将检验首席研究员 F. Ivy Carroll 博士开发的新型可卡因 3-苯基托烷类似物。这些化合物具有暗示药物治疗价值的特性；它们有效且选择性地与多巴胺转运蛋白结合，多巴胺转运蛋白是一个众所周知的参与可卡因行为效应的位点，并且具有起效缓慢和持续时间长的作用，这些属性被认为是有效治疗可卡因成瘾的药物所必需的。 项目 3 将研究一组这些化合物对大鼠静脉注射可卡因自我给药的影响，并为灵长类动物自我给药研究（项目 4）提供信息。我们的实验室在这一过程方面经验丰富，目前正在进行此类研究。项目 3 的第一个目标是评估所选择的六种化合物（每种两种剂量），因为它们能够概括可卡因判别线索，同时对响应率的干扰最小（从项目 2 获得的结果）。我们将检查这些化合物是否会改变可卡因自我给药的维持。结果将导致在项目 4 中选择要测试的四种化合物。所选择的化合物将提供可卡因剂量反应函数的下移，因为这是基于在动物中获得的自我给药数据的可卡因成瘾有效药物治疗剂的最佳指标。项目 3 的第二个目标是检查两种化合物对可卡因的杠杆按压反应消失后可卡因诱导的反应恢复的影响。这个程序是一个完善的“复发”模型，是在我们的实验室建立和运行的。项目3的目标2的具体结果是确定复合块是否引起恢复或引起恢复。从该目标获得的数据将与项目 2 和 4 的结果结合使用，为继续进行人体研究的决定提供信息。 （项目 5 和 6）。