EXTRACELLULAR NEUROCHEMISTRY AND SUBSTANCE ABUSE

描述(改编自申请人的摘要)： 已知在人类中有重大滥用责任的几种物质 与大脑的黑质纹状体和中脑边缘多巴胺通路相互作用。 这类物质的例子包括可卡因、苯丙胺和苯环利定。 详细了解这些药物影响多巴胺能的方式 因此，传递对于理解 物质滥用的基础机制。例如，理解这些 机制是开发新的药物治疗策略的前提 施虐者。 本申请的目的是调查滥用物质是如何 影响体内多巴胺浓度的时空分布 接受多巴胺能神经支配的大脑结构的细胞外空间。 这种分布是由多巴胺释放动力学调节的，分子 扩散和多巴胺摄取。因此，存在一种可能性，即药物 可能不仅会改变细胞外空间中的多巴胺水平，还会改变 它的时空分布。关于多巴胺能这方面的信息 目前还不存在传输。 这项研究将使用多巴胺选择性微型传感器进行 提供高空间和高时间分辨率。有了这些设备， 药物对血药浓度时空分布调控的影响 尾状核和核细胞外间隙中的多巴胺 观察大鼠的伏隔。

DESCRIPTION(Adapted from applicant's abstract): Several substances with significant abuse liability in man are known to interact with the nigrostriatal and mesolimbic dopamine pathways of the brain. Examples of such substances include cocaine, amphetamine, and phencyclidine. Detailed knowledge of the manner in which these drugs affect dopaminergic transmission is, therefore, of central importance in understanding the mechanisms that underlie substance abuse. For instance, understanding those mechanisms is a prerequisite for developing new therapeutic strategies for drug abusers. The objective of this application is to investigate how substances of abuse affect the spatiotemporal distribution of dopamine concentrations in the extracellular space of brain structures that received dopaminergic innervation. That distribution is regulated by the kinetics of dopamine release, molecular diffusion, and dopamine uptake. The possibility exists, therefore, that drugs might change not just the level of dopamine in the extracellular space but also it spatiotemporal distribution. Information on this aspect of dopaminergic transmission does not presently exist. This research will be conducted by using dopamine-selective microsensors that offer both high spatial and high temporal resolution. With these devices, the impact of drugs on the regulation of the spatiotemporal distribution of dopamine in the extracellular space of the caudate nucleus and nucleus accumbens of the rat will be observed.