NEURONAL MEDIATION OF ETHANOL INDUCED TASTE AVERSIONS

该奖项的申请者是一名体验式动物行为研究 研究酒精性质或酒精的科学家，他使用几种 行为范式。他的直接职业目标是超越 酒精相关行为的行为分析与职业生涯的开始 研究风险决定因素所涉及的生物学机制 因为酗酒。这笔赠款中概述的培训计划将 对应聘者实现目标至关重要 通过为他提供一套独特的解剖检查技能 与酒精有关的神经元通路的分子生理学 厌恶效应以及这些效应如何与盈利相互作用以影响 寻酒行为。因此，他将制定一项科学的 这将使他成为一个真正的竞争行为 神经学家正在寻找他的长期职业目标--获得一种 学术教员职位。大学里的培训环境 包括华盛顿大学各系的实验室和教职员工 心理学和精神病学。除了课程和技术 培训期间，指导委员会将为申请者提供定期 在整个项目中进行输入和反馈。中概述的假设 目前的建议旨在研究神经化学途径。 调节对酒精的厌恶特性和酒精诱导的 条件性味道厌恶(CTA)。之前的研究，使用类似CFO的 免疫反应性(CFLI)作为细胞活化的指标，有 研究表明，被认为与味觉有关的脑干区域 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 关于脑干中的细胞活动与 酒精摄入和CTA表达：a)酒精的来源是什么 神经元对脑干的输入，导致这种细胞激活和 哪一种可能调节味觉厌恶的学习？为了研究这个问题， 电解性损伤将在特定的大脑区域和 在NTS和CTA获得/表达中对cFLI的后续影响 将会被评估。B)细胞的神经化学表型是什么？ 由酒精和味觉激活的脑干 要酒吗？原位杂交双标记技术 将使用组织化学和免疫组织化学来检测这一点 问题。以及C)，哪些神经递质和受体负责 在NTS中调节这种细胞活动，这些是 神经递质系统与味觉厌恶学习有关？这 这个问题将通过使用特定的受体拮抗剂和 受体放射自显影。更好地了解神经元 与乙醇相关的厌恶效应的基础机制 可能会让人更准确地预测出 酒精中毒，并可能有助于药理学的发展 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.