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释放的指标，是 需要在完整动物身上进行监测，以补充使用损伤进行的研究 产生行为缺陷的多巴胺能系统。 监测DA释放问题的一种方法是使用 代谢物水平作为DA释放的指标。为了使用代谢物 信息有效地，细胞外水平之间的关系 代谢产物对神经递质的释放必须是已知的。在现在 提出胞外二羟基苯乙酸二羟基苯乙酸相互关系模型 酸(DOPAC)对多巴胺的释放进行了描述和几个实验 提出了对模型进行检验的建议。特别是，体内伏安法将是 用于测定多巴胺向胞外代谢的动力学 DOPAC。这种方法代表了一种新的、非药理学的方法 研究神经递质释放的调节。的速率常数 DOPAC的形成及其从细胞外空间的清除将是 下定决心。这将通过对伏安数据进行非线性回归来实现 代表细胞外DOPAC在非常短的时间内增加 电刺激黑质纹状体多巴胺能通路。这个 伏安数据将由高性能液体进行验证 细胞外液的层析。的相对时间进程 细胞外DOPAC中多巴胺的释放和变化将通过 关于使用代谢物信息作为一种 神经递质释放的时间指标。此外，基本面 完整黑质纹状体多巴胺能系统的动力学信息 将获得任何其他方法不可能获得的。

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. Additionally, fundamental information on the dynamics of the intact nigrostriatal dopaminergic system will be obtained that is not possible to acquire by any other method.