The neurologic consequences of ethanol intoxication and alcoholism exact an immense social, psychological, medical, and economic price on this nation. Ethanol appears to produce important neurologic and behavioral effects by interacting with neural cell membranes and disrupting the activity of many membrane-dependent biochemical systems. Brain opioid systems may mediate some of ethanol's central nervous system effects. Cell culture offers an attractive means to characterize the interaction of ethanol with opioid receptors in living, homogeneous, neural cells, isolated from secondary neural, endocrine, and cardiopulmonary influences. Using the neural cell line, NG108-15, I have shown that ethanol produces striking changes in delta-opioid receptros, and have examined several possible responsible mechanisms. The proposed studies will improve the model system by using stationary, differentiated cells cultured in serum-free, hormonally-defined medium, continue to define the molecular mechanisms underlying ethanol's effects on delta-opioid receptors, and determine the functional consequences of opioid receptor changes on cAMP and cGMP metabolism. This research seeks ultimately to characterize molecular events underlying ethanol intoxication, tolerance, and physical dependence; such knowledge will advance the search for biological markers in patients at risk for alcoholism, and more rational therapy for those already affected.
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