Ethanol abuse and dependence continue to be a serious public health issue, with much associated morbidity and mortality. The biopsychosocial causes of alcoholism are complex; however, the current literature indicates that anxiolysis is prominent in the reinforcing effect of alcohol. Many investigators are currently using animal models to elucidate the biological substrates of anxiogenesis and anxiolysis. These studies now indicate a significant role for the amygdala in mediating these phenomena, and suggest that the amygdala is the most appropriate model system for investigating the physiological substrates of ethanol-mediated anxiolysis. In spite of this groundwork, few studies have addressed effects of ethanol on amygdala physiology. As ethanol effects are specific for brain regions and neuron types, only a study of direct ethanol effects in the amygdala will provide this informa on. The present proposal will use state-of-the-art electrophysiological techniques to investigate effects of ethanol in the amygdala brain slice preparation. Although ethanol in relevant concentrations likely acts at multiple neuronal sites, it still retains a remarkably high degree of specificity. The most consistent findings are effects on synaptic transmission and voltage-sensitive ion channels. This proposal will include investigations of interactions between ethanol and voltage-dependent currents, synaptic transmission, and synaptic plasticity. The results of this proposal have potential applications in several areas. By examining physiological effects of alcohol with a specific focus on mechanisms underlying the anxiolytic and anxiogenic actions, this study may direct future clinical studies on causes and treatment of alcoholism. This study also may elucidate mechanisms involved in development of anxiety disorders and seizure disorders. Finally, the proposed work will provide critical groundwork needed to assess the role of specific neurotransmitters in ethanol-induced anxiolysis and to investigate the long-term effects associated with repeated ethanol use.
