Innovations for In Vivo Neurochemical Analysis

申请人描述：这个实验室最近的努力已经产生了 细胞外空间神经化学监测的创新技术 哺乳动物的大脑。具体地说，体内监测的新策略 多巴胺、谷氨酸、胆碱、葡萄糖、抗坏血酸和氧气 精心设计的。过去对这些装置的研究是在麻醉状态下进行的 大鼠和脑片中。本申请描述了以下的适配 脑组织中多巴胺和谷氨酸的检测新技术 清醒动物纹状体的细胞外间隙。 据信，抑制从细胞外间隙摄取多巴胺的药物 导致细胞外多巴胺水平的增加，而这种增加是 被认为是可卡因作用机制的重要组成部分。 然而，先前的电生理学数据表明，摄取抑制剂 关闭多巴胺的释放，这表明细胞外的减少 多巴胺水平是意料之中的。我们将检验可卡因的假设 使用一种新的药物导致细胞外多巴胺水平的下降 体内神经化学结果的量化策略。 大脑皮层谷氨酸能活动的降低与 精神分裂症，这就需要监测细胞外的谷氨酸 接受皮质投射的大脑结构的空间。我们将测试 假设细胞外谷氨酸的神经源性成分 纹状体的水平受内侧前额叶皮质的调节。

APPLICANT'S DESCRIPTION: Recent efforts in this laboratory have produced innovative technologies of neurochemical monitoring in the extracellular space of the mammalian brain. Specifically, new strategies of the in vivo monitoring of dopamine, glutamate, choline, glucose, ascorbate, and oxygen have been devised. Past research with these devices has been conducted in anesthetized rats and in brain slices. The present application describes the adaptation of the new techniques to the detection of dopamine and glutamate in the extracellular space of the striatum in awake animals. Drugs that inhibit dopamine uptake from the extracellular space are believed to cause an increase in extracellular dopamine levels, and this increase is regarded as an important component of the mechanism of action of cocaine. Nevertheless, prior electrophysiological data suggest that uptake inhibitors shut down dopamine release, which suggests that a decrease in extracellular dopamine levels is to be expected. We will test the hypothesis that cocaine administration leads to a decrease in extracellular dopamine levels using a new strategy for the quantification of in vivo neurochemical results. A decrease in glutamatergic activity of the cortex is heavily implicated in schizophrenia, which creates a need to monitor glutamate in the extracellular space of brain structures that receive cortical projections. We will test the hypothesis that the neuronally derived component of extracellular glutamate levels in the striatum is under the regulation of the medial prefrontal cortex.