COCAINE USE & MONOAMINE FUNCTION IN NON HUMAN PRIMATES

可卡因的使用

• 批准号: 8172303
• 负责人: LEONARD L HOWELL
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172303
• 关键词: Affinity; Amphetamines; Behavior; Behavioral; Cocaine; Cocaine Abuse; Cocaine Dependence; Computer Retrieval of Information on Scientific Projects Database; Dopamine; Dose; Effectiveness; Funding; Glutamates; Grant; Human; Institution; Intravenous; Modeling; Motor; Neuropharmacology; Pharmaceutical Preparations; Property; Relative (related person); Research; Research Personnel; Resources; Self Administration; Serotonin; Source; United States National Institutes of Health; analog; behavioral pharmacology; cocaine use; extracellular; in vivo; inhibitor/antagonist; monoamine; neurochemistry; nonhuman primate; postsynaptic; serotonin receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is a critical need to develop effective medications to treat cocaine addiction. Medication effectiveness in reducing cocaine use was determined in a nonhuman primate model of intravenous drug self-administration. The project continued to focus on the behavioral pharmacology and in vivo neurochemistry of monoamine transporter inhibitors as complementary approaches to characterize the neuropharmacology of cocaine. In addition, we have emphasized behavioral and neurochemical interactions between glutamate and dopamine. More recently, we have conducted studies with a variety of monoamine releasers having different affinity for dopamine and serotonin receptors. PAL-353, which is more selective for releasing dopamine relative to serotonin, induced robust behavioral-stimulant effects similar to those observed for amphetamine. In contrast, PAL-313, which is equipotent in releasing both dopamine and serotonin, did not induce behavioral-stimulant effects over a broad range of doses. These differences in profile of behavioral effects were evident even at drug doses that markedly increased extracellular dopamine, supporting the interpretation that an increase in serotonergic tone can have a postsynaptic inhibitory effects on motor behavior. We are currently characterizing the reinforcing effectiveness of several amphetamine analogs that differ in potency to release dopamine and serotonin. The results indicate that compounds with high potency for serotonin release have a behavioral profile of low abuse liability. The integration of in vivo neurochemistry and behavioral pharmacology in nonhuman primates will define neurochemical mechanisms that underlie the addictive properties of cocaine and related stimulants. The results obtained will direct efforts to treat cocaine abuse in humans.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 迫切需要开发有效的药物来治疗可卡因成瘾。在静脉注射药物自我给药的非人类灵长类动物模型中确定了减少可卡因使用的用药效率。该项目继续关注单胺转运蛋白抑制剂的行为药理学和体内神经化学，作为表征可卡因神经药理学的补充方法。此外，我们强调了谷氨酸和多巴胺之间的行为和神经化学相互作用。 最近，我们对多巴胺和5-羟色胺受体有不同亲和力的多种单胺释放剂进行了研究。 PAL-353对于释放多巴胺相对于5-羟色胺更有选择性，引起了与苯丙胺观察到的相似的鲁棒行为刺激作用。相反，在释放多巴胺和5-羟色胺方面是等值的PAL-313，并未在广泛的剂量中诱导行为刺激的作用。即使在药物剂量明显增加细胞外多巴胺的药物剂量下，这些行为影响方面的差异也很明显，这支持了以下解释：血清素能张力的增加可以对运动行为产生突触后抑制作用。我们目前正在表征几种释放多巴胺和5-羟色胺效力的几种苯丙胺类似物的增强有效性。 结果表明，具有高效力的5-羟色胺释放的化合物具有低虐待责任的行为特征。非人类灵长类动物中体内神经化学和行为药理学的整合将定义可卡因和相关兴奋剂上瘾特性的神经化学机制。获得的结果将指导治疗人类可卡因滥用的努力。