ETHANOL EFFECTS ON CNS TISSUE IN VIVO & IN VITRO

这是对二级研究科学家发展的请求 奖品。乙醇暴露对哺乳动物中枢神经系统的影响 神经系统功能将通过使用细胞外细胞外 和细胞内记录在完整的脑原位，在 体外脑片和眼内脑移植。研究将会 关注表现与酒精相关的差异的遗传变异 作为研究急性酒精行为的模型系统的行为 以及研究对酒精的耐受性和依赖性。这个 这项研究计划的长期目标有三个方面。 第一，乙醇的电生理反应机制 将被描述为直接的、调节的或涉及局部的 环路中间神经元。第二，对乙醇反应的变化，如 以及神经递质系统的功能变化，将是 在诱导容忍或依赖之后决定的。最后， 利用遗传变异，酒精诱导的电生理 反应将与酒精诱导的行为相关。一个 更好地理解乙醇如何改变中枢神经系统功能 为酒精中毒和酒精中毒问题提供新的见解 酗酒。在我的RSDA二级奖项的任期内，我的 专业成长计划包括加强与 实验室的数量。1)我将扩展与 丹佛和博尔德的当地酒精调查人员，2)我将访问 致卡罗林斯卡研究所实验室的拉尔斯·奥尔森博士 瑞典斯德哥尔摩将继续描述颅内和 眼内脑移植作为分离脑回路的模型 研究急性和慢性乙醇的作用并结合研究 酒精对大脑发育的影响。我要去拜访罗伊医生 加拿大蒙特利尔康科迪亚大学的WISE学习 自我给药与药物研究的行为学方法 偏好。我将在退伍军人管理局与约翰·卡布博士共度时光 俄勒冈州波特兰医院研究服务学习方法 研究酒精依赖。我将扩大我的合作 与瑞典乌普萨拉大学的奥洛夫·托特马尔博士 继续研究乙醇和乙醇之间的相互作用 单胺代谢物以及缩合产物。最后， 我会和王云医生一起在国防医疗工作 台湾中心继续我们对西格玛和卡帕的研究 鸦片的作用机制。通过这些合作、访问和 讨论我希望扩大在我的 研究乙醇的实验室；特别是在体内1)领域 电化学，2)慢性单元记录，3)高性能 4)遗传和选择育种；5) 细胞内记录。我目前的工作主要集中在 急性和慢性乙醇的电生理效应 曝光。关于未来的方向，我也想 继续研究乙醇偏好的机制和 依赖性，以及乙醇对人体健康影响的研究 出生前和出生后的大脑发育。

This is a request for a level II Research Scientist Development Award. The effects of ethanol exposure on mammalian central nervous system function will be pursued using both extracellular and intracellular recording in the intact brain in situ, in the in vitro brain slice and in intraocular brain transplants. Studies will focus on genetic variants manifesting differential alcohol-related behaviors as model systems for examing acute ethanol actions as well as for studying tolerance and dependence to alcohol. The long-term objectives of this research program are three fold. First, the mechanism of electrophysiological responses to ethanol will be characterized as direct, modulatory or involving local circuit interneurons. Second, changes in responses to ethanol, as well as functional changes in neurotransmitter systems, will be determined after induction of tolerance or dependence. Finally, using the genetic variants, ethanol-induced electrophysiological responses will be correlated with alcohol-induced behaviors. A greater understanding of how ethanol alters CNS function should furnish new insights into the problems of alcohol intoxication and alcoholism. During the tenure of my RSDA level II award, my professional growth plans include augmented interactions with a number of laboratories. 1) I will extended collaborations with local alcohol investigators in Denver and in Boulder, 2) I will visit to the laboratory Dr. Lars Olson at the Karolinska Institute in Stockholm, Sweden to continue characterizing intracranial and intraocular brain grafts as models of isolated brain circuits to study acute and chronic ethanol actions and to combine to study the effects of ethanol on brain development. I will visit Dr. Roy Wise at Concordia University in Montreal, Canada to learn behavioral Methods for studying self administration and drug preference. I will spend time with Dr. John Carbbe at the VA Hospital Research Service in Portland, Oregon to learn methods of studying ethanol dependence. I will extend my collaboration with Dr. Olof Tottmar at the University of Uppsala in Sweden to continue our studies of interactions between ethanol and monoamine metabolites as well as condensation products. Finally, I will work with Dr. Yun Wang at the National Defense Medical Center in Taiwan to continue our studies of sigma and kappa opiate mechanisms. Through these collaborations, visits and discussions I hope to expand the methodology used in my laboratory to study ethanol; specifically in the areas of 1) in vivo electrochemistry, 2) chronic unit recording, 3) high performance liquid chromotgraphy, 4) genetics and selective breeding, and 5) intracellular recording. My present work concentrates on the electrophysiological effects of acute and chronic ethanol exposure. In terms of future directions, I would also like to pursue studies of the mechanisms of ethanol preference and dependence, as well as investigations of the effects of ethanol on pre- and postnatal brain development.