G-Protein Regulation of Ethanol Action

G 蛋白对乙醇作用的调节

• 批准号: 7127656
• 负责人: MICHAEL Scott BOWERS
• 金额: $ 4.88万
• 依托单位: ERNEST GALLO CLINIC AND RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-16 至 2008-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127656
• 关键词: G protein; alcoholic beverage consumption; alcoholism /alcohol abuse; behavioral /social science research tag; behavioral genetics; craving; ethanol; laboratory rat; neurochemistry; pharmacokinetics; postdoctoral investigator; relapse /recurrence; substance abuse related behavior

Relapse remains problematic for alcoholics due, in part to the lack of effective pharmacotherapies. Identification of the precise molecular entities that contribute to relapse may facilitate rational drug design. Recent findings indicate a role of molecules that modulate signaling through G-proteins in relapse. This proposal focuses on the Activator of G-protein Signaling (AGS3). AGS3 expression increases during withdrawal from repeated cocaine administration. High AGS3 expression appears to induce neurochemistry resembling that found in addicted animals and AGS3 expression appears to increase the propensity to relapse to cocaine seeking behavior. AGS3 expression also increases in vitro after repeated ethanol exposure and in vivo after withdrawal from repeated ethanol administration. The role of AGS3 in alcoholism, however, remains to be elucidated. This proposal will determine the role of AGS3 and its signaling partner Gbetagamma in both the genetic and behavioral impact of repeated ethanol administration. Our objective is to determine if AGS3 contributes to relapse to ethanol seeking behavior. Our findings may aid pharmaceutical development for individuals suffering from alcoholism and alcohol abuse.

对于酗酒者来说，复发仍然是一个问题，部分原因是缺乏有效的药物疗法。识别导致复发的精确分子实体可能有助于合理的药物设计。 最近的研究结果表明，通过 G 蛋白调节信号传导的分子在复发中发挥着重要作用。该提案重点关注 G 蛋白信号传导激活剂 (AGS3)。在重复使用可卡因后戒断期间，AGS3 表达增加。高 AGS3 表达似乎会诱导类似于成瘾动物中发现的神经化学反应，并且 AGS3 表达似乎会增加可卡因寻求行为复发的倾向。 AGS3 表达在体外重复暴露于乙醇后以及在体内停止重复乙醇给药后也会增加。然而，AGS3 在酗酒中的作用仍有待阐明。该提案将确定 AGS3 及其信号伙伴 Gbetagamma 在重复乙醇施用的遗传和行为影响中的作用。我们的目标是确定 AGS3 是否会导致乙醇寻求行为复发。我们的研究结果可能有助于针对酗酒和酒精滥用患者的药物开发。