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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 该项目旨在确定介导酒精对大脑的急性和长期作用的分子机制。确定酒精的分子靶点对于制定预防酒精滥用的策略以及设计酒精成瘾疗法至关重要。使用急性制备的小脑切片中颗粒细胞的膜片钳记录来识别对急性酒精暴露的分子和细胞反应。具体来说，我们测试了四种分子机制的作用，这些机制已知与小脑中的 GABA 能系统相互作用，在介导酒精诱导的酒精浓度增加中的作用。 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，​​从而导致成瘾。最后，我们确定小脑颗粒细胞对酒精敏感性的个体差异是否是对酒精引起的运动障碍敏感性个体差异的基础。众所周知，对酒精引起的运动障碍的敏感性是人类酒精滥用的遗传预测因素，因此确定其分子基础应该有助于筛查人类是否有酒精滥用的倾向。对已完成实验的分析将提高我们的 了解酒精的分子靶标，并将确定小脑对酒精滥用和成瘾的贡献的分子方面。