Proteomic Approaches to Alcoholism

酗酒的蛋白质组学方法

• 批准号: 6929684
• 负责人: HOWARD B GUTSTEIN
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929684
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; amygdala; behavioral /social science research tag; brain metabolism; drug addiction; drug habituation; laboratory rat; neuropsychological tests; neuropsychology; pathologic process; proteomics; reinforcer; relapse /recurrence; self medication

DESCRIPTION (provided by applicant): Critical issues for improving the treatment of alcoholism are what neurobiological changes are responsible for the transition from non-dependent alcohol use to alcoholism, and what persistent changes mediate relapse. The goals of the present proposal are to begin to explore the neurobiological mechanisms responsible for alcohol escalation and to begin to define the mechanisms responsible for relapse. To achieve these goals, we will test the following hypotheses: 1) Sufficient exposure to alcohol leads to changes in specific elements of the extended amygdala that produce elevations in the hedonic set point. In turn, this leads to progressive elevation in ethanol intake and a propensity to relapse during abstinence. 2) Self-administration of ethanol coupled with passive administration causes changes in protein expression levels and function more characteristic of the addictive process than passive administration alone. To test these hypotheses, we propose studies with the following Specific Aims: 1) To examine the effects of ethanol dependence on protein expression and modification with a focus on changes associated with ethanol reinforcement. 2) To determine long-lasting changes in protein expression and modification associated with vulnerability to relapse upon re-exposure to ethanol. Our proposed combination of cutting-edge behavioral, neuroanatomical, and proteomic approaches will permit the identification of important molecular targets that should enable the development of more specific and effective pharmacotherapy both to help block the process of alcohol addiction and prevent relapse in those suffering from alcoholism.

描述（由申请人提供）：改善酒精中毒治疗的关键问题是神经生物学的变化是导致从非依赖性酒精使用到酒精中毒的过渡，而持续变化的变化介导了复发。本提案的目标是开始探索负责酒精升级的神经生物学机制，并开始定义负责复发的机制。 为了实现这些目标，我们将检验以下假设： 1）足够的酒精暴露会导致延长杏仁核的特定元素的变化，这些杏仁核的特定元素在享乐设定点中产生升高。反过来，这导致乙醇摄入量的逐渐升高和戒酒期间复发的倾向。 2）乙醇和被动给药的自我给药会导致蛋白质表达水平的变化和功能在上瘾过程中比单独的被动给药更具特征。 为了检验这些假设，我们提出了以下具体目的的研究： 1）检查乙醇依赖对蛋白质表达和修饰的影响，重点是与乙醇增强相关的变化。 2）确定蛋白质表达的长期变化和与重新暴露乙醇复发有关的脆弱性相关的变化。 我们提出的尖端行为，神经解剖学和蛋白质组学方法的结合将允许鉴定重要的分子靶标，这些靶标应该能够发展更具体有效的药物疗法，既可以帮助阻止酒精成瘾的过程又可以防止患有酒精中毒的人的复发。