GABAERGIC ADAPTATION IN ETHANOL TOLERANCE & DEPENDENCE

该提案是对ADAMHA RSDA II级支持的请求 对于Gerald D.Frye，博士，与R01 AA06322密切相关 弗莱博士就是私家侦探。这一奖项将允许弗莱博士 大学及院系服务的责任及 减少教学，这样他至少可以申请 90%的时间用于研究和专业发展。那些 弗莱博士不再需要的部门资源 支持将用于招聘一名额外的教职员工 与酒精和药物滥用有关的生化研究兴趣 问题。弗莱博士的研究努力将继续集中在 GABAA和GABAB受体/转导复合体的作用 酒精中毒的发生、耐受性和体力 依赖。正在测试的假设是，“急性或 酒精的慢性作用部分依赖于增加或 GABA受体作为突触的有效性分别降低 换能器。研究旨在评估 乙醇处理对GABAA和GABAB模型大鼠生理的影响 受体系统。弗莱博士不仅会继续他的研究 使用豚鼠回肠，但他将扩大他的研究范围 通过学习新的神经生理技术对大鼠进行训练 海马区切片通过与Dr. 威廉·格里菲斯。提供更多培训机会和新的 研究应该来自其他领域的计划合作 其中GABA受体与乙醇的相互作用可能是 乙醇中毒的根本原因。在这方面，初步 与凯利·海斯特博士的合作(心血管生理学 和高血压)；Jack Nations博士(重金属毒性和 乙醇偏好)；以及尚未受雇于 离子通道生物化学系。这些新的计划 培训和加强跨学科研究协作 应该会显著促进弗莱博士的专业发展 作为一名对生物医学的影响感兴趣的基础科学家 乙醇。

This proposal is a request for an ADAMHA RSDA level II support for Gerald D. Frye, Ph.D. and closely related to R01 AA06322 on which Dr. Frye is the PI. This award will allow Dr. Frye's responsibilities for University and Department service and teaching to be reduced so that he will be able to apply at least 90% of his time to research and professional development. Those departmental resources that are no longer required for Dr. Frye's support will be used to recruit an additional faculty member with biochemical research interests related to alcohol and drug abuse questions. Dr. Frye's research efforts will continue to focus on the role that GABAA and GABAB receptor/transducer complexes play in the genesis of ethanol intoxication, tolerance and physical dependence. The hypothesis being tested is that, "acute or chronic actions of ethanol depend in part on increased or decreased efficacy of GABA receptors, respectively, as synaptic transducers". Studies are designed to evaluate the influence of ethanol treatment on the physiology of model GABAA and GABAB receptor systems. Not only will Dr. Frye continue his research using the guinea pig ileum but he will broaden his research training by learning new neurophysiological techniques in the rat hippocampal slice through an important collaboration with Dr. William Griffith. Additional opportunities for training and new research should come form other planned collaborations in areas where a GABA receptor-ethanol interaction could be an underlying cause of ethanol toxicity. In this regard preliminary collaborations with Dr. Kelly Hester (cardiovascular physiology and hypertension); Dr. Jack Nations (heavy metals toxicity and ethanol preference); and and individual yet to be hired by the Department (ion channel biochemistry). These plans for new training and increased interdisciplinary research collaboration should significantly enhance Dr. Frye's professional development as a basic scientist interested in the biomedical impact of ethanol.