ETHANOL EFFECTS ON CNS TISSUE IN VIVO & IN VITRO

这是一个二级研究科学家发展的要求 奖 乙醇暴露对哺乳动物中枢神经系统的影响 神经系统功能将使用细胞外 和细胞内记录在完整的大脑原位，在 体外脑切片和眼内脑移植。 研究将 重点关注表现出与酒精有关的差异的遗传变异 行为作为模型系统，用于检查急性乙醇作用， 以及研究对酒精的耐受性和依赖性。 的 该研究计划的长期目标有三个方面。 第一，乙醇引起的电生理反应的机制 将被描述为直接的、调节性的或涉及局部的 回路中间神经元 第二，对乙醇的反应变化， 以及神经递质系统的功能变化， 在诱导耐受性或依赖性后决定的。 最后， 使用遗传变异，乙醇诱导的电生理 反应将与酒精诱导的行为相关。 一 更深入地了解乙醇如何改变中枢神经系统功能， 为酒精中毒问题提供新的见解， 酒精中毒 在我的RSDA二级奖的任期内，我的 专业成长计划包括增强与 实验室数量。 1)我将扩大与 丹佛和博尔德的当地酒精调查员，2）我将访问 卡罗林斯卡医学院的拉尔斯·奥尔森博士 瑞典斯德哥尔摩继续表征颅内和 眼内脑移植物作为孤立脑回路的模型， 研究急性和慢性乙醇作用并将其联合收割机 酒精对大脑发育的影响 我会去看罗伊医生 怀斯在加拿大蒙特利尔的康考迪亚大学学习 研究自我管理和药物的行为方法 偏好 我会和退伍军人管理局的约翰·卡布医生一起 医院研究服务在波特兰，俄勒冈州学习方法 研究乙醇依赖性。 我会扩大我的合作 与瑞典乌普萨拉大学的奥洛夫·托特马尔博士一起， 继续研究乙醇和 单胺代谢物以及缩合产物。 最后， 我将和王云博士一起在国防医疗中心工作 在台湾的中心继续我们的研究sigma和kappa 鸦片机制 通过这些合作、访问和 我希望扩大我的讨论中使用的方法， 研究乙醇的实验室;特别是在1）体内 电化学，2）慢性单位记录，3）高性能 液相色谱法，4）遗传学和选择性育种，以及5） 细胞内记录 我目前的工作集中在 急性和慢性乙醇的电生理效应 exposure. 至于未来的发展方向，我亦希望 研究乙醇偏好的机制， 依赖性，以及乙醇对 产前和产后的大脑发育。

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.