COCAINE USE & MONOAMINE FUNCTION IN NON HUMAN PRIMATES

可卡因的使用

• 批准号: 8357376
• 负责人: LEONARD L HOWELL
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357376
• 关键词: Adverse effects; Agonist; Attenuated; Behavior; Behavioral; Biological Assay; Cocaine; Cocaine Dependence; Development; Dopamine; Drug Addiction; Effectiveness; Funding; Goals; Grant; Human; Mediating; Mental disorders; National Center for Research Resources; Pharmaceutical Preparations; Pharmacotherapy; Primates; Principal Investigator; Procedures; Relapse; Research; Research Infrastructure; Resources; Role; SB 242084; Saimiri; Self Administration; Serotonin; Serotonin Receptor 5-HT2C; Source; System; Therapeutic; United States National Institutes of Health; Work; cocaine use; cost; drug abuser; drug seeking behavior; in vivo; m chlorophenylpiperazine; monoamine; neurochemistry; non-drug; nonhuman primate; pre-clinical research; stimulant abuse; therapeutic development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is a critical need to develop effective medications to treat cocaine addiction. The project continues to focus on behavioral and in vivo neurochemical interactions between serotonin and cocaine in the context of self-administration behavior in nonhuman primates. The long-term goal is to identify pharmacotherapeutic targets for the treatment of cocaine addiction and relapse. We are currently working to examine the role of the serotonin 5-HT2C receptor subtype. To date, our results indicate that systemic administration of the preferential 5-HT2C receptor agonist m-chlorophenylpiperazine (mCPP) or the selective 5-HT2C receptor agonist Ro 60-0175 attenuates the behavioral-stimulant and reinforcing effects of cocaine in squirrel monkeys. Importantly, both compounds reduce drug-seeking behavior in the reinstatement procedure, a preclinical research assay with relevance to relapse in human drug abusers. Additionally, Ro 60-0175 has demonstrated the capacity to selectively alter drug-seeking behavior while sparing other nondrug-mediated behaviors, indicative of a minimal side effect profile. Interestingly, SB 242084 potentiates cocaine-primed reinstatement. Hence, 5-HT2C receptors can bidirectionally modulate the behavioral effects of cocaine. Collectively, the results obtained during the previous year have important implications concerning the effectiveness of serotonergic systems as potential targets for the development of pharmacotherapies to treat stimulant abuse. Moreover, serotonin has significant therapeutic potential in the treatment of a variety of psychiatric disorders. Accordingly, the elucidation of basic neurochemical interactions between serotonin and dopamine in vivo in nonhuman primates should have significant impact on the development of therapeutics outside the field of drug addiction.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 迫切需要开发有效的药物来治疗可卡因成瘾。该项目继续关注在非人类灵长类动物自我管理行为的背景下，血清素和可卡因之间的行为和体内神经化学相互作用。长期目标是确定治疗可卡因成瘾和复吸的药物靶点。我们目前正在研究5-羟色胺5-HT 2C受体亚型的作用。迄今为止，我们的研究结果表明，全身给予优先5-HT 2C受体激动剂间氯苯哌嗪（mCPP）或选择性5-HT 2C受体激动剂Ro 60-0175减弱了松鼠猴中可卡因的行为刺激和强化作用。重要的是，这两种化合物都减少了恢复过程中的药物寻求行为，这是一种与人类药物滥用者复发相关的临床前研究测定。 此外，Ro 60-0175已证明能够选择性改变药物寻求行为，同时保留其他非药物介导的行为，表明副作用最小。有趣的是，SB 242084增强可卡因引发的恢复。因此，5-HT 2C受体可以双向调节可卡因的行为效应。总的来说，在过去的一年中获得的结果有重要的影响有关的有效性，肾上腺素能系统作为潜在的目标，为发展药物治疗兴奋剂滥用。此外，5-羟色胺在治疗各种精神障碍方面具有显著的治疗潜力。因此，在非人灵长类动物体内血清素和多巴胺之间的基本神经化学相互作用的阐明应该有显着的影响，药物成瘾领域以外的治疗方法的发展。