DOPAMINE FUNCTION IN MIDBRAIN

中脑的多巴胺功能

• 批准号: 6233841
• 负责人: LOUIS A CHIODO
• 金额: $ 18.78万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233841
• 关键词: G protein; RNase protection assay; action potentials; biological signal transduction; developmental neurobiology; dopamine; dopamine receptor; dopamine transporter; electrophysiology; embryo /fetus tissue /cell culture; embryo /fetus toxicology; enkephalins; flow cytometry; gene expression; high performance liquid chromatography; immunocytochemistry; in situ hybridization; laboratory rat; membrane transport proteins; mesencephalon; neuropharmacology; neurotransmitter biosynthesis; neurotransmitter transport; newborn animals; northern blottings; pregnancy; receptor binding; receptor sensitivity; substance P; teratogens; tyrosine 3 monooxygenase

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.

在子宫内暴露于乙醇的动物和人类表现出改变的运动 活动和提高唤醒。 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被产前乙醇暴露改变。 本提案中详细说明的初步意见表明， 假设是正确的。 该提案详细说明了对以下方面的全面审查： 子宫内乙醇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， 在突触前多巴胺神经元和突触后多巴胺敏感神经元中 细胞 这些分析将包括详细调查 多巴胺神经元的数量和形态，多巴胺细胞的评价 电生理学（放电频率和模式），检查变化 在各种多巴胺受体（多巴胺自身受体，D2和D1 受体），检查改变的G蛋白mRNA表达，分析 P物质和甲硫氨酸-脑啡肽mRNA表达的变化，以及 多巴胺转运体 结合电生理学， 免疫组织化学、生物化学和药理学方法将 就业。 希望获得的结果将提供新的 关于乙醇对表达的影响的信息 中脑多巴胺神经元系统的正常成人特征。