RELATIONSHIP OF EXTRACELLULAR DOPAC TO DOPAMINE RELEASE

为了了解多巴胺（DA）释放与 行为，研究中，DA释放，或DA释放的指数， 需要在完整动物中进行监测，以补充使用病变的研究 多巴胺能系统产生行为缺陷。 一种解决监测DA释放问题的方法是使用 代谢物水平作为DA释放的指标。 为了利用代谢产物 信息有效，细胞外水平的关系， 必须知道代谢物到神经递质的释放。 本 提出了一种细胞外二羟基苯乙酸 酸（DOPAC）多巴胺释放的描述和几个实验， 并对模型进行了检验。 特别地，体内伏安法将是 用于确定多巴胺代谢到细胞外的动力学 DOPAC。 这种方法代表了一种新的非药理学方法， 研究神经递质释放的调节。 速率常数 DOPAC的形成及其从细胞外间隙的清除将是 测定 这将通过对伏安数据的非线性回归来完成 代表细胞外DOPAC的增加， 黑质纹状体多巴胺能通路的电刺激。 的 伏安数据将通过高效液相色谱法进行验证。 细胞外液的层析。 相对时间进程 多巴胺释放和细胞外DOPAC的变化将用 关于使用代谢物信息作为 神经递质释放的时间指数。

In order to understand the relationship of dopamine (DA) release to behavior, studies in which DA release, or an index of DA release, is monitored in intact animals are needed to complement studies using lesions of dopaminergic systems to produce behavioral deficits. One approach to the problem of monitoring DA release has been to use metabolite levels as indices of DA release. In order to use metabolite information effectively, the relationship of the extracellular levels of the metabolite to neurotransmitter release must be known. In the present proposal a model of the relationship of extracellular dihydroxyphenylacetic acid (DOPAC) to dopamine release is described and several experiments to test the model are proposed. In particular, in vivo voltammetry will be used to determine the kinetics of dopamine metabolism to extracellular DOPAC. This approach represents a new, nonpharmacological method for studying the regulation of neurotransmitter release. Rate constants for formation of DOPAC and its clearance from the extracellular space will be determined. This will be done by nonlinear regression on voltammetric data representing the increase in extracellular DOPAC following very brief electrical stimulation of the nigrostriatal dopaminergic pathway. The voltammetric data will be validated by high performance liquid chromatography of the extracellular fluid. The relative time course of dopamine release and change in extracellular DOPAC will be examined with regard to the use and limitations of using metabolite information as a temporal index of neurotransmitter release.