ROLE OF OPIATES IN ALCOHOL-INDUCED NEUROTOXICITY

阿片类药物在酒精引起的神经毒性中的作用

• 批准号: 3112920
• 负责人: DIPAK KUMAR SARKAR
• 金额: $ 10.88万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3112920
• 关键词: acetaldehyde; alcoholism /alcohol abuse; biological models; biological signal transduction; calcium; cytotoxicity; dopamine; dopamine receptor; drug adverse effect; drug tolerance; drug withdrawal; embryo /fetus tissue /cell culture; endorphins; ethanol; hypothalamus; isoquinolines; laboratory rat; messenger RNA; neurons; neurotoxins; prolactin; radioimmunoassay; secretion; verapamil

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.

已知中枢阿片肽参与神经系统和 酗酒的行为并发症。 涉及的细胞机制 由于乙醇调节的阿片类药物活性目前难以捉摸 缺乏可靠的实验模型系统。 本提案的目标 是为了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 乙醇的长期治疗对β-内啡肽的分泌， 神经元活力和形态； b) 代谢的影响 乙醇对β-内啡肽分泌、神经元活力和 形态学; c) 对阿片类药物合成的分子调控的影响 急性和慢性乙醇及其代谢物治疗后。 将通过放射免疫测定法测量肽，并通过 mRNA 水平 通过RNA保护测定法测定。 本研究将：1）建立 含β-内啡肽的分泌和合成程度如何 培养物中的神经元受到乙醇的影响； 2）阐明急性的、适应性的 和戒断反应，3）确定代谢影响 乙醇对阿片肽的作用。 此外，它可能有助于 开发新方法来理解乙醇的机制 对阿片肽的作用，并可能表明有效的治疗方法 乙醇引起的神经毒性。