G-Protein Regulation of Ethanol Action

G 蛋白对乙醇作用的调节

• 批准号: 7162960
• 负责人: MICHAEL Scott BOWERS
• 金额: $ 5.04万
• 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/7162960
• 关键词: Acute; Adenosine; Adenosine A2 Receptors; Adrenergic Receptor; Agonist; Alcohol consumption; Alcoholism; Alcohols; Animals; Beds; Behavior; Behavioral; Behavioral Genetics; Brain region; Cell Nucleus; Cells; Cocaine; Condition; Corpus striatum structure; Cues; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Data; Development; Diamond; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Dose; Drug Design; Ethanol; Evaluation; Fellowship; GTP-Binding Proteins; Gases; Gene Expression; Genes; Genetic Transcription; Goals; Immunoblotting; In Vitro; Individual; Injection of therapeutic agent; Knowledge; Laboratories; Laboratory Study; Light; Luciferases; Measures; Mediating; Methods; Modeling; Molecular; Names; Neurons; Nucleus Accumbens; Odors; Peptides; Pharmaceutic Aids; Pharmacotherapy; Phosphotransferases; Production; Protein Overexpression; Proteins; Receptor Activation; Regulation; Relapse; Reporter; Reporting; Role; Self Administration; Signal Transduction; Testing; Thinking; Up-Regulation; Withdrawal; Work; alcohol cue; alcohol effect; alcohol exposure; alcohol relapse; alcohol seeking behavior; alcohol sensitivity; alcoholism/alcohol abuse; cellular engineering; craving; deprivation; drug seeking behavior; extracellular; human RASD1 protein; in vivo; intraperitoneal; knock-down; neurochemistry; novel; problem drinker; reinforcer; research study; response; stem

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.

由于缺乏有效的药物疗法，由于缺乏有效的药物，酗酒者的复发仍然存在问题。鉴定有助于复发的精确分子实体可能有助于合理的药物设计。 最新发现表明，通过G蛋白在复发中调节信号传导的分子的作用。该提案侧重于G蛋白信号传导的激活因子（AGS3）。 AGS3的表达在从重复可卡因施用中提取期间增加。高AGS3表达似乎诱导了与成瘾动物发现的神经化学相似，而AGS3表达似乎增加了人们寻求可卡因的倾向。 AGS3表达在反复接触乙醇后反复暴露和体内在反复给予乙醇后的体外也会增加体外。然而，AGS3在酒精中毒中的作用尚待阐明。该建议将确定AGS3及其信号伴侣Gbetagamma在重复乙醇给药的遗传和行为影响中的作用。我们的目标是确定AGS3是否有助于复发乙醇寻求行为。我们的发现可能有助于患有酗酒和酗酒的人的药物开发。

项目成果

Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence.

• DOI: 10.1016/j.neuron.2010.02.015
• 发表时间: 2010-03-11
• 期刊: NEURON
• 影响因子: 16.2
• 作者: Hopf, F. Woodward;Bowers, M. Scott;Chang, Shao-Ju;Chen, Billy T.;Martin, Miguel;Seif, Taban;Cho, Saemi L.;Tye, Kay;Bonci, Antonello
• 通讯作者: Bonci, Antonello