Neurobiol mechanism/acupuncture therapy/alcoholism

描述（由申请人提供）：酒精滥用和酒精中毒在美国和世界各地构成严重的社会和经济问题。尽管酒精中毒的药物治疗方法越来越多，但目前的治疗方法成功率有限，复发率高。尽管针灸在缓解酒精渴望方面显示出令人鼓舞的效果，但导致这种效果的机制尚不清楚。我们的长期目标是了解针灸治疗酒精中毒的神经生物学原理。本研究的目的是确定酒精戒断和针刺对大鼠腹侧被盖区（VTA）多巴胺神经元（一个药物滥用的奖励中心）的影响。其核心假设是，针刺可逆转或减弱由慢性乙醇给药戒断引起的多巴胺神经元兴奋性下降，从而恢复多巴胺系统的“正常”功能。针刺引起的变化可在脑切片中检测到。我们计划通过追求以下两个具体目标来检验我们的假设并实现本申请的目标：1。确定乙醇戒断对脑切片多巴胺神经元的影响。2. 确定针刺对乙醇戒断引起的改变的影响。研究设计和方法：为了达到这些目的，我们将对从慢性酒精给药中退出的大鼠进行针灸/假针灸。虽然对戒断的行为反应将在体内进行检查，但神经元活动将在VTA脑切片上进行检查，使用膜片钳技术。这项提议的工作是创新的，因为它将使用经过验证的现代技术来阐明针灸及其在治疗酒精成瘾中的作用机制。这种方法有望产生以下结果：它将确定乙醇戒断对大脑切片中多巴胺神经元的影响；优化针刺参数改变乙醇戒断诱导的神经元反应，阐明针刺对慢性乙醇戒断大鼠多巴胺神经元的影响。这一新知识将对我们对针灸如何工作的理解产生重大影响。这些知识的应用有望提高针灸治疗酒精成瘾的有效性。

DESCRIPTION (provided by applicant): Alcohol abuse and alcoholism pose serious social and economic problems in the United States and around the world. Despite the increasing number of pharmacotherapies for alcoholism, current treatments have limited success and high rates of relapse. Although acupuncture has shown promising results in alleviating alcohol craving, the mechanism causing this effect remains unclear. Our long-range goal is to understand the neurobiological principles underlying acupuncture therapy for alcoholism. The objective of this proposal is to identify the changes induced by alcohol withdrawal and by acupuncture in rat dopamine neurons of the ventral tegmental area (VTA), a reward center of drug abuse. The central hypothesis is that acupuncture reverses or attenuates the reduction in excitability of dopamine neurons induced by the withdrawal of chronic ethanol administration and thus restores "normal" function of the dopamine system The changes caused by acupuncture can be detected in brain slices. We plan to test our hypothesis and accomplish the objective of this application by pursuing the following two Specific Aims: 1. Identify effects of ethanol withdrawal on dopamine neurons in brain slices. 2. Identify effects of acupuncture on alterations induced by ethanol withdrawals. Research design and methods: To achieve these aims, acupuncture/sham acupuncture will be given to rats withdrawn from chronic alcohol administration. While behavioral responses to withdrawal will be examined in vivo, the neuronal activities will be examined on VTA brain slices, using patch clamp techniques. The proposed work is innovative, because it will use proven modern techniques to elucidate the mechanisms of both acupuncture and its use in treating alcohol addiction. This approach is expected to yield the following outcomes: it will identify the effects of ethanol withdrawal on dopamine neurons in brain slices; optimize parameters of acupuncture to alter the neuronal responses induced by ethanol withdrawal, and elucidate changes induced by acupuncture in dopamine neurons of rats withdrawn from chronic ethanol administration. This new knowledge will have a major impact on our understanding of how acupuncture works. The application of this knowledge is expected to improve the effectiveness of acupuncture treatment in alcohol addiction.