ACTIONS OF ALCOHOL IN PRIMATE CEREBELLUM

酒精对灵长类动物小脑的作用

• 批准号: 8173273
• 负责人: KATHLEEN A GRANT
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173273
• 关键词: Acute; Alcohol abuse; Alcohol consumption; Alcohols; Brain; Cerebellum; Chronic; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Grant; Human; Individual; Institution; Mediating; Molecular; Molecular Target; Primates; Research; Research Personnel; Resources; Role; Slice; Source; System; Testing; United States National Institutes of Health; Withdrawal Symptom; addiction; alcohol exposure; alcohol sensitivity; alcoholism therapy; chronic alcohol ingestion; granule cell; improved; motor impairment; patch clamp; prevent; research study; response; therapy design; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is aimed at determining the molecular mechanisms that mediate acute and long term actions of alcohol on the brain. Identifying the molecular targets of alcohol is fundamental to developing strategies for preventing the development of abusive use of alcohol, and for designing therapies for alcohol addiction. Patch-clamp recordings from granule cells in acutely prepared slices of cerebellum were used to identify molecular and cellular responses to acute alcohol exposure. Specifically, we tested the role of four molecular mechanisms, which are known to interact with the GABAergic system in the cerebellum, in mediating the alcohol-induced increase in cerebellar granule cell GABAergic transmission. We will determined if chronic, voluntary alcohol consumption leads to long-term molecular adaptations in cerebellar GABAergic transmission. Molecular adaptation to chronic alcohol consumption may contribute to withdrawal symptoms, and hence contribute to addiction. Finally, we determined if individual variability in cerebellar granule cell sensitivity to alcohol underlies individual variability in sensitivity to alcohol-induced motor impairment. Sensitivity to alcohol-induced motor impairment is known to be a heritable predictor of alcohol abuse in humans, and thus determining its molecular underpinnings should help screen humans for predilection for alcohol abuse. Analysis of completed experiments will improve our understanding of the molecular targets of alcohol, and will identify molecular aspects of cerebellar contribution to alcohol abuse and addiction.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目旨在确定酒精对大脑的急性和长期作用的分子机制。确定酒精的分子靶标对于制定防止滥用酒精的发展战略和设计酒精成瘾治疗方法至关重要。急性制备的小脑切片中颗粒细胞的膜片钳记录被用来识别急性酒精暴露的分子和细胞反应。具体地说，我们测试了四种已知与小脑中GABA能系统相互作用的分子机制在调节酒精诱导的 小脑颗粒细胞GABA能传递。我们将确定长期自愿饮酒是否会导致小脑GABA能传递的长期分子适应。对长期饮酒的分子适应可能有助于 戒断症状，并因此导致成瘾。最后，我们确定了小脑颗粒细胞对酒精敏感性的个体差异性是否是酒精引起的运动损伤敏感性的个体差异性的基础。众所周知，对酒精引起的运动损伤的敏感性是人类酗酒的可遗传预测因素，因此确定其分子基础应该有助于筛查人类酗酒的倾向。对已完成实验的分析将改善我们的 了解酒精的分子靶点，并将确定小脑对酒精滥用和成瘾的分子方面的贡献。