ROLE OF OPIATES IN ALCOHOL-INDUCED NEUROTOXICITY

已知中枢阿片肽参与神经系统， 酒精中毒的行为并发症 涉及的细胞机制 在乙醇调节的阿片活性是难以捉摸的，因为目前 缺乏可靠的实验模型系统。 这项提案的目的是 是确定乙醇和下丘脑之间的相互作用 阿片肽β-内啡肽，通过使用新开发的方法， 在原代培养物中维持分离的胎儿下丘脑神经元。 将进行研究以确定：a）急性和慢性炎症的影响， 慢性乙醇治疗对β-内啡肽分泌的影响， 神经元活力和形态; B） 乙醇对β-内啡肽分泌、神经元活力和 形态学; c）对阿片样物质合成的分子调节的影响 急性和慢性乙醇及其代谢物治疗后。 肽将通过放射免疫测定法测量，mRNA水平将通过放射免疫测定法测量。 通过RNA保护试验测定。 本研究将：1）建立 β-内啡肽的分泌和合成 培养的神经元受到乙醇的影响; 2）阐明急性，适应性 和戒断反应，以及3）确定代谢的影响， 乙醇对阿片肽的作用。 此外，它可能有助于 开发新的方法来理解乙醇的机制 阿片肽的作用，并可能表明有效的治疗方法， 乙醇诱导的神经毒性。

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.