COCAINE AND COCAINE ANALOGS--IN VIVO MICRODIALYSIS

近年来合成了大量的取代可卡因类似物 多年来，已经允许结构活性分析的机制， 可卡因与多巴胺转运蛋白结合， 在体外，这一过程被认为是行为兴奋剂的核心， 加强可卡因的特性。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， 在效力和选择性方面不同可卡因类似物 在这些部位升高体内细胞外多巴胺水平是 饶有兴趣最近，研究人员报道了一种 抑制多巴胺摄取和多巴胺转运蛋白的可卡因类似物 在体外以高亲和力结合，但缺乏行为学上的 可卡因的刺激和辨别刺激特性。的影响 这种化合物和其他可卡因类似物对细胞外多巴胺 体内水平未知。本提案的目的是解决 中脑边缘多巴胺神经递质相互作用的重要性 可卡因的行为和神经化学作用的系统， 体内结构相关的类似物。为此， 设计用于比较以下药物的效力和功效： 作为体外多巴胺摄取抑制剂的可卡因和可卡因类似物 其提高细胞外多巴胺的效力和功效， 来刺激体内的自发活动。

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.