NEURONAL MEDIATION OF ETHANOL INDUCED TASTE AVERSIONS

该奖项的申请人是一位经验丰富的动物行为研究 一位研究酒精特性的科学家， 行为模式 他的职业目标是超越 对酒精相关行为进行行为分析，然后开始职业生涯 研究与风险决定因素有关的生物学机制 因为酗酒 该补助金中概述的培训计划将 对申请人实现其目标至关重要 通过给他提供一套独特的解剖学技能 以及酒精相关神经通路的分子生理学 厌恶效应以及这些效应如何与收入相互作用， 酗酒行为 因此，他将开发一种科学的 这将使他成为一个真正有竞争力的行为 神经科学家，因为他寻求他的长期职业目标，获得一个 学术职位。 大学的培训环境 华盛顿的实验室包括实验室和院系， 心理学和精神病学。 除了课程和技术 培训，指导委员会将为申请人提供定期 在整个项目中的输入和反馈。 中概述的假设 目前的建议旨在研究神经化学途径， 调节对酒精的厌恶性和酒精诱导的 条件性味觉厌恶（CTA） 以前的研究，使用类cFos 免疫反应性（cFLI）作为细胞活化的指示， 表明脑干区域被认为与味觉有关， 厌恶学习（特别是孤束核 （NTS））被酒精和与之配对的味道激活。 这种药。 拟议的实验旨在评估以下内容 关于脑干细胞活动的问题， 酒精管理和CTA表达：A）什么是来源 脑干的神经元输入导致这种细胞激活， 可能介导味觉厌恶学习？ 为了研究这个问题， 电解损伤将在特定的大脑区域进行， 对NTS和CTA采集/表达中cFLI的后续影响 将被评估。B）在神经细胞中的神经化学表型是什么？ 脑干被酒精和味觉激活， 酒吗？ 原位杂交双标记法 组织化学和免疫组织化学将用于检查这一点 问题 C）哪些神经递质和受体负责 来调节NTS的细胞活动， 与味觉厌恶学习有关的神经递质系统这 这个问题将通过使用特异性受体拮抗剂和 受体放射自显影 更好地理解神经元 与乙醇相关的厌恶效应的基础机制 可以让人们更准确地预测 酒精中毒，并可能是有益的发展药理学 旨在防止酗酒的治疗。

The applicant of this award is an experience animal behavior research scientist who has studied the properties or alcohol using several behavioral paradigms. His immediate career goal is to go beyond the behavioral analysis of alcohol-related behaviors and begin a career investigating the biological mechanisms involved in determinants of risk for alcohol abuse. The training program outlined in this grant would be critically important for allowing the applicant to reach his goals by providing him with a unique set of skills for examining the anatomy and molecular physiology of neuronal pathways involved in alcohol's aversive effects and how these interact with earning to influence alcohol-seeking behavior. As a result, he will develop a scientific identity which will make him a truly competitive behavioral neuroscientist as he seeks his long-term career goal of obtaining an academic faculty position. The training environment at the University of Washington includes laboratories and faculty in the Departments of Psychology and Psychiatry. In addition to courses and technical training, a steering committee will provide the applicant with regular input and feedback throughout the project. The hypotheses outlined in the present proposal are designed to examine the neurochemical pathways that mediate the aversive properties to alcohol and alcohol-induced conditioned taste aversions (CTA). Previous research, using cFos-like immunoreactivity (cFLI) as an indication of cellular activation, has shown that the brainstem regions thought to be involved in taste aversion learning (particularly, the nucleus of the solitary tract (NTS)) are activated by alcohol and by tastes that have been paired with this drug. Proposed experiments are designed to assess the following questions about the cellular activity in the brainstem associated with alcohol administration and CTA expression: A) What are the sources of neuronal input to the brainstem which cause this cellular activation and which may mediate taste aversion learning? To examine this question, electrolytic lesions will be made in specific brain regions and subsequent effects on cFLI in the NTS and CTA acquisition/expression will be assessed. B) What is the neurochemical phenotype of cells in the brainstem that are activated by alcohol and by tastes paired with alcohol? Double-labeling-procedures with in situ hybridization histochemistry and immunohistochemistry will be used to examine this question. And C), What neurotransmitters and receptors are responsible for mediating this cellular activity in the NTS, and are these neurotransmitter systems involved with taste aversion learning? This question will be addressed by using specific receptor antagonists and receptor autoradiography. A better understanding of the neuronal mechanisms that underlie the aversive effects associated with ethanol may allow one to more accurately predict the predisposition towards alcoholism, and may be useful for the development of pharmacological treatments targeted at preventing alcohol abuse.