Neurobiol mechanism/acupuncture therapy/alcoholism

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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 Research design and methods: To achieve these aims, acupuncture/sham acupuncture will be given to rats withdrawn from chronic alcohol administration.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responses induced by ethanol withdrawal, and elucidate changes induced by acupuncture in dopamine neurons of rats withdrawn from chronic ethanol administration.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.