COCAINE USE & MONOAMINE FUNCTION IN NON HUMAN PRIMATES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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给药行为的背景下，5-羟色胺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发的药物治疗目标。我们目前正在研究5-羟色胺5-HT2C受体亚型的作用。到目前为止，我们的结果表明，全身给予优先的5-HT2C受体激动剂间氯苯基哌嗪(MCPP)或选择性的5-HT2C受体激动剂RO60-0175可以减弱可卡因对松鼠猴子的行为刺激和增强作用。重要的是，这两种化合物都减少了恢复过程中的寻求药物行为，这是一种与人类吸毒者复发相关的临床前研究分析。 此外，RO60-0175已经证明了有选择地改变药物寻找行为的能力，同时避免了其他非药物介导的行为，表明副作用最小。有趣的是，SB 242084增强了可卡因诱导的复原力。因此，5-HT2C受体可以双向调节可卡因的行为效应。总体而言，前一年取得的结果对5-羟色胺能系统作为治疗兴奋剂滥用药物疗法开发的潜在靶点的有效性具有重要影响。此外，5-羟色胺在治疗各种精神疾病方面具有显著的治疗潜力。因此，阐明非人灵长类动物体内5-羟色胺和多巴胺之间的基本神经化学相互作用将对药物成瘾以外的治疗方法的发展产生重大影响。

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.