Brain Biomarkers of Alcoholism and Abstinence

酗酒和禁欲的大脑生物标志物

基本信息

批准号：
7247245
负责人：
HOWARD B GUTSTEIN
金额：
$ 43.29万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-15 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7247245
关键词：
Abstinence Acute Air Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcoholism Alcohols Amygdaloid structure Animals Behavior Disorders Behavior Therapy Behavioral Biological Markers Brain Brain region Cells Characteristics Chronic Complex Condition Consumption Corticotropin-Releasing Hormone Coupled Data Data Analyses Dependence Development Disruption Elements Elevation Ethanol Ethanol dependence Excision Exposure to Functional disorder GABA Agonists Gel Goals Hour Intake Laboratories Lead Mediating Methods Modeling Modification Neurobiology Pharmacotherapy Phase Preparation Process Proteins Proteomics Rattus Recording of previous events Relapse Rewards Sampling Self Administration Solutions Structure System Techniques Testing Training Withdrawal Work addiction alcohol abuse therapy alcohol exposure alcohol reinforcement clinically relevant hedonic improved interest laser capture microdissection neurobiological mechanism neurochemistry novel prevent protein expression vapor

项目摘要

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 delineate brain biomarkers that indicate the neurobiological mechanisms responsible for alcohol escalation and to define brain biomarkers associated with 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 biomarkers 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。本提案的目标是描述指示导致酒精升级的神经生物学机制并定义与复发相关的脑生物标志物的神经生物学机制。为了实现这些目标，我们将测试以下假设：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会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生物标志物，这些生物标志物应能够发展出更具体有效的药物疗法，以帮助阻止酒精成瘾的过程并防止患有酒精中毒的人的复发。