BEHAVIORAL EFFECTS OF NIGRAL D1 ANTAGONISM

大量证据表明黑质网状部 (SNr)作为直接和间接连接的输出区域 起源于几个纹状体区域。 SNr包含非常高的 多巴胺（DA）D1受体的浓度，以及详细的解剖结构 DA受体的细胞定位研究已经证明 D1受体存在于含GABA的纹状体黑质末梢上， 在SNr. 拟议的研究旨在确定SNr是否是 一些行为效应的重要解剖学作用部位 D1拮抗剂 此外，拟议的研究将调查 DA和GABA在SNr中的相互作用。 它是假设 将D1拮抗剂SCH 23390局部注射到SNr中， 相对于注射其他药物， 大脑部位 此外，假设D1拮抗作用将降低 通过微透析测量SNr GABA释放，以及 黑质内输注SCH 23390将被联合逆转， 给予GABA-A激动剂蝇蕈醇。 的结果予以 实验可以帮助修改当前的解剖学观点， D1拮抗作用行为效应的神经化学基础，以及 可以扩展我们对行为意义的认识， SNr中树突状释放的DA。这些概念具有重要的 对我们理解病理生理学的影响 帕金森氏病中多巴胺耗竭的意义，并可能有助于 以确定新的治疗策略， 帕金森症状

Considerable evidence indicates that substantia nigra pars reticulata (SNr) acts as an output area for direct and indirect connections originating from several striatal regions. SNr contains a very high concentration of dopamine (DA) D1 receptors, and detailed anatomical studies of the cellular localization of DA receptors have demonstrated that D1 receptors are present on GABA-containing striatonigral terminals in SNr. The proposed research is designed to determine if SNr is an important anatomical site of action for some of the behavioral effects of D1 antagonists. In addition, the proposed research will investigate the interaction between DA and GABA in SNr. It is hypothesized that local injections of the D1 antagonist SCH 23390 into SNr will be highly potent at producing behavioral effects relative to injections in other brain sites. Also, it is hypothesized that D1 antagonism will decrease SNr GABA release as measured by microdialysis, and that the effects of intra-nigral infusions of SCH 23390 will be reversed by co- administration of the GABA-A agonist muscimol. The results of these experiments could help to modify current views on the anatomical and neurochemical basis of the behavioral effects of D1 antagonism, and could expand our knowledge of the behavioral significance of dendritically released DA in SNr . These concepts have important implications for our understanding of the pathophysiological significance of dopamine depletions in Parkinson's disease, and may help to identify novel therapeutic strategies for the treatment of parkinsonian symptoms.