COCAINE AND COCAINE ANALOGS--IN VIVO MICRODIALYSIS

可卡因和可卡因类似物——体内微透析

• 批准号: 2390993
• 负责人: BRYAN K TOLLIVER
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2390993
• 关键词: analog; benztropine; chordate locomotion; cocaine; dopamine; extracellular; laboratory rat; mazindol; microdialysis; neuropharmacology; nucleus accumbens

The synthesis of a large series of substituted cocaine analogs in recent years has allowed structure-activity analysis of the mechanisms by which cocaine binds to the dopamine transporter and inhibits dopamine uptake in vitro, a process considered central to the behavioral stimulant and reinforcing properties of cocaine. Because cocaine interacts with other sites in the brain which may potentiate its actions on dopamine neurons, the ability of cocaine analogs which differ in potency and selectivity at these sites to elevate extracellular dopamine levels in vivo is of great interest. Recently investigators have reported the synthesis of a cocaine analog which inhibits dopamine uptake and dopamine transporter binding in vitro with high affinity, but which lacks the behavioral stimulant and discriminative stimulus properties of cocaine. The effects of this compound and other cocaine analogs on extracellular dopamine levels in vivo are unknown. The objective of this proposal is to address the importance of neurotransmitter interactions in mesolimbic dopamine systems on the behavioral and neurochemical effects of cocaine and structurally related analogs in vivo. To this end the experiments described below are designed to compare the potencies and efficacies of cocaine and cocaine analogs as inhibitors of dopamine uptake in vitro with their potencies and efficacies to elevate extracellular dopamine and to stimulate locomotor activity in vivo.

近年来一大系列取代可卡因类似物的合成 几年来，已经能够对其机制进行结构-活性分析 可卡因与多巴胺转运体结合，抑制多巴胺摄取 在体外，这一过程被认为是行为刺激剂和 可卡因的增强特性。因为可卡因与其他 大脑中可能增强其对多巴胺神经元作用的部位， 效力和选择性不同的可卡因类似物的能力 在体内这些部位提高细胞外多巴胺水平是 非常感兴趣。最近，调查人员报道了一种合成一种 可卡因类似物，抑制多巴胺摄取和多巴胺转运蛋白 体外结合具有高亲和力，但缺乏行为 可卡因的刺激性和辨别性刺激性。其影响 该化合物和其他可卡因类似物对细胞外多巴胺的影响 体内的水平尚不清楚。这项提议的目标是解决 中脑边缘多巴胺中神经递质相互作用的重要性 关于可卡因和可卡因的行为和神经化学效应的系统 体内结构相关的类似物。为此，这些实验 下面描述的是设计用来比较 可卡因及其类似物体外抑制多巴胺摄取的实验研究 它们能提高细胞外多巴胺的活性和效率 以刺激体内的运动活动。