DOPAMINE FUNCTION IN MIDBRAIN

子宫内暴露于乙醇的动物和人类表现出运动改变 活动和更多的唤醒。基于广泛的临床和 临床前文献表明，这些功能是 受中脑多巴胺(DA)系统的影响，我们假设 这些神经系统可能会因出生前接触酒精而改变。 这项提案中详细的初步观察表明，这 假设是正确的。这份提案详细说明了对 宫内酒精暴露对多巴胺神经元系统的影响。 它概述了一系列相互关联的研究，这些研究将考察变化 突触前多巴胺神经元和突触后多巴胺敏感神经元 细胞。这些分析将包括对 多巴胺神经元的数量和形态及对多巴胺细胞的评价 电生理学(放电率和模式)、变化检查 在不同的多巴胺受体(多巴胺自身受体，D2和D1 受体)，检测改变的G蛋白mRNA表达，分析 P物质和甲硫氨酸脑啡肽mRNA的表达，并检测 多巴胺转运体。结合电生理， 免疫组织化学、生化和药理学方法将 受雇的。希望所获得的发现将提供新的 关于乙醇对基因表达影响的信息 正常成人的中脑多巴胺神经系统特征。

Animals and humans exposed to ethanol in utero exhibit altered motor activity and increased arousal. Based on an extensive clinical and preclinical literature which indicates that these functions are influenced by mesencephalic dopamine (DA) systems, we hypothesized that these neuronal systems might be altered by prenatal ethanol exposure. Preliminary observations detailed within this proposal indicate that this hypothesis was correct. This proposal details a complete examination of the influence of in utero ethanol exposure on dopamine neuronal systems. It outlines a series of interrelated studies which will examine changes in both presynaptic dopamine neurons and postsynaptic dopamine-sensitive cells. The analyses will include the detailed investigation of the number and morphology of dopamine neurons, evaluation of dopamine cell electrophysiology (firing rate and pattern), examination of the changes in various dopamine receptors (dopamine autoreceptors, D2 and D1 receptors), examination of altered G-protein mRNA expression, analysis of substance P and met-enkephalin mRNA expression, and examination of the dopamine transporter. Combined electrophysiological, immunohistochemical, biochemical and pharmacological methods will be employed. It is hoped that the findings obtained will provide new information regarding the influence of ethanol on the expression of normal adult characteristics of mesencephalic dopamine neuronal systems.