Neurobiol mechanism/acupuncture therapy/alcoholism

描述(申请人提供)：酗酒和酗酒在美国和世界各地造成严重的社会和经济问题。尽管治疗酒精中毒的药物疗法越来越多，但目前的治疗方法效果有限，复发率高。尽管针灸在缓解酒精渴求方面显示出了令人振奋的效果，但导致这种效果的机制尚不清楚。我们的长期目标是了解酒精中毒针灸疗法背后的神经生物学原理。本研究旨在探讨酒精戒断和针刺对药物滥用奖赏中枢腹侧被盖区(VTA)多巴胺能神经元的影响。中心假说是，针刺可逆转或减弱慢性酒精注射引起的多巴胺神经元兴奋性降低，从而恢复多巴胺系统的“正常”功能。针刺引起的变化可在脑片中检测到。我们计划通过以下两个具体目标来验证我们的假设并实现这一应用的目标：1.确定乙醇戒断对脑片中多巴胺神经元的影响。2.确定针刺对酒精戒断所致的改变的影响。研究设计和方法：为了达到这些目的，将对戒断酒的大鼠进行针刺/假针刺。虽然对戒断的行为反应将在体内进行检测，但神经元活动将在VTA脑片上使用膜片钳技术进行检测。这项拟议的工作具有创新性，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。这一方法有望产生以下结果：它将识别酒精戒断对脑片中多巴胺神经元的影响；优化针灸参数以改变酒精戒断诱导的神经元反应，并阐明针刺对慢性酒精戒断大鼠多巴胺神经元的影响。这一新知识将对我们理解针灸的工作原理产生重大影响。这一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 Research design and methods: To achieve these aims, acupuncture/sham acupuncture will be given to rats withdrawn from chronic alcohol administration.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.