Synaptosomal Protein Changes After EtOH Self-Administration

EtOH 自我给药后突触体蛋白的变化

• 批准号: 6953375
• 负责人: Frank A Witzmann
• 金额: $ 21.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6953375
• 关键词: alcoholism /alcohol abuse; brain mapping; dendrites; dopamine; ethanol; gene expression; laboratory rat; neural information processing; neural plasticity; neuropharmacology; nucleus accumbens; protein purification; protein quantitation /detection; proteomics; reinforcer; self medication; synapses; synaptosomes; tegmentum

DESCRIPTION (provided by applicant): The goals of this application are to better understand alterations in the neural circuitry underlying the reinforcing actions of ethanol (EtOH). The overall hypothesis is that self-administration of EtOH within the posterior ventral tegmental area (VTA) produces downstream alterations that enhance synaptic function and promote the reinforcing effects of EtOH. Previous studies from our laboratory indicated that Wistar and alcohol-preferring (P) rats will self-infuse EtOH directly into the posterior VTA, whereas the anterior VTA does not support this behavior. In addition, the reinforcing effects of EtOH within the posterior VTA requires activation of DA neurons, and presumably involves information processing in VTA target regions. In this proposal, the effects of EtOH self-infusion into the posterior VTA on changes in protein expression in targeted limbic brain regions will be examined. Preliminary data indicated that P rats self-infusing EtOH into the posterior VTA showed increases in the expression of genes for proteins involved in neurite and dendritic spine outgrowth, suggesting increased synaptic function has developed in the nucleus accumbens (Acb) as a result of EtOH activation of VTA DA neurons. The present proposal will continue the initial study by examining changes in expression of synaptic proteins following EtOH self-administration into the posterior VTA using state-of-the-art proteomics analysis coupled to subcellular fractionation techniques to obtain samples of the Acb enriched in synaptic components.

描述（由申请人提供）：本申请的目标是更好地了解乙醇（ETOH）加强作用的神经回路的改变。总体假设是，在后腹侧侧侧区域（VTA）内ETOH的自给量会产生下游变化，从而增强突触功能并促进ETOH的增强作用。我们实验室的先前研究表明，Wistar和饮酒（P）大鼠将直接自输入ETOH到后VTA中，而前VTA不支持这种行为。此外，ETOH在后VTA中的增强作用需要激活DA神经元，并且大概涉及VTA目标区域中的信息处理。在此提案中，将研究ETOH自发输入后VTA对靶向边缘大脑区域蛋白质表达变化的影响。初步数据表明，p大鼠自我输入ETOH进入后VTA显示出涉及神经突和树突状脊柱生长的蛋白质表达的增加，这表明由于EtOH活化的结果，突触功能的增加已在核核（ACB）中发展出来。 vta da神经元。本提案将通过检查ETOH自我接合后的突触蛋白表达的变化来继续进行初步研究。