ROLE OF OPIATES IN ALCOHOL-INDUCED NEUROTOXICITY

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Central opioid peptides are known to be involved in the neurological and behavioral complications of alcoholism. The cellular mechanism involved in ethanol-regulated opioid activity is elusive at present because of a lack of reliable experimental model systems. The goal of this proposal is to determine the interaction between ethanol and the hypothalamic opioid peptide Beta-endorphin, by using a newly developed method for maintaining isolated fetal hypothalamic neurons in primary cultures. Studies will be conducted to determine: a) the effect of acute and chronic treatments of ethanol on the secretion of Beta-endorphin, neuronal viability and morphology; b) the metabolic influences of ethanol action on Beta-endorphin secretion, neuronal viability and morphology; c) the effect on molecular regulation of opioid synthesis following acute and chronic ethanol and its metabolite treatments. Peptides will be measured by radioimmunoassay, and mRNA levels will be determined by RNA protection assay. This study will: 1) establish to what extent the secretion and synthesis of Beta-endorphin-containing neurons in culture is affected by ethanol; 2) elucidate acute, adaptive and withdrawal responses, and 3) identify the metabolic influences of ethanol action on the opioid peptide. Furthermore, it may help in developing novel approaches to understanding the mechanisms of ethanol action on opioid peptides, and may indicate effective therapies for ethanol-induced neurotoxicity.