Striatal Mechanisms of Ethanol Seeking

寻找乙醇的纹状体机制

• 批准号: 7919251
• 负责人: Patricia H. Janak
• 金额: $ 35.09万
• 依托单位: ERNEST GALLO CLINIC AND RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7919251
• 关键词: Address; Alcohol consumption; Alcohol dependence; Alcohols; Animals; Attenuated; Behavior; Behavioral; Behavioral Mechanisms; Corpus striatum structure; Cues; Development; Dopamine; Dorsal; Ethanol; Fire - disasters; Glutamates; Goals; Habits; Human; Intake; Knowledge; Lateral; Learning; Maintenance; Measures; Medial; Mediating; Microinjections; Modeling; Neural Pathways; Neurobiology; Neurons; Neurotransmitters; Obsessive compulsive behavior; Operant Conditioning; Oral; Outcome; Performance; Pharmaceutical Preparations; Play; Procedures; Process; Psychological reinforcement; Rattus; Relapse; Reliance; Rewards; Role; Self Administration; Signal Transduction; Site; Stimulus; Sucrose; System; Testing; Time; Training; Work; addiction; alcohol abuse therapy; alcohol effect; alcohol reward; alcohol seeking behavior; base; environmental change; experience; habit learning; public health relevance; relating to nervous system; research study; response; theories; therapy design

DESCRIPTION (provided by applicant): Habitual behavior does not require an explicit representation of the goal, but is triggered by automatic responses to the stimuli that previously were paired with alcohol reward. The exact time course of this transition has not been defined for alcohol self-administration, however, there are well-defined tests for whether instrumental behavior is goal-directed or habitual that can be used to determine whether or not self-administration is habitual. The current proposal seeks to test the hypothesis that alcohol self-administration after extended training will display the hallmarks of a habitual behavior. As conditioned cues also play a major role in relapse, we will also test the effects of alcohol-predictive cues after extended alcohol self-administration training. The reliance of alcohol-seeking, including that promoted by cues, on dorsal striatal circuitry will be probed. PUBLIC HEALTH RELEVANCE: It has long been hypothesized that alcohol- and drug-seeking becomes habitual over time; this is apparent in our colloquial use of the term `drug habit'. Therefore, understanding the transition of ethanol self-administration from goal-directed to habitual may provide information on the neurobiology that underlies the transition from casual ethanol use to addiction. These results will provide new information on the role of specific neural pathways in alcohol self-administration and increase our understanding of the behavioral mechanisms that underlie its intake. Therefore, these experiments will address an important lack in our basic knowledge of the neurobiology of alcohol addiction that will allow us to better design therapies for alcohol abuse.

描述（由申请人提供）：习惯行为不需要明确表示目标，而是由对先前与酒精奖励配对的刺激的自动响应触发的。但是，尚未将这种过渡的确切时间过程定义为酒精自我管理，但是，有明确定义的测试对于工具行为是指向目标定向还是可以用来确定自我管理是否习惯性的测试。当前的提案旨在检验以下假设：在扩展培训后的酒精自我管理将表现出习惯行为的标志。由于条件提示在复发中也起着重要作用，因此我们还将在扩展酒精自我管理训练后测试酒精预测性线索的影响。将探测寻求酒精的依赖，包括提示在背纹状体回路上促进的酒精。 公共卫生相关性：长期以来一直假设饮酒和寻求毒品随着时间的流逝而成为习惯。这在我们对“毒品习惯”一词的通俗使用中显而易见。因此，了解乙醇从目标定向到习惯的过渡可能会提供有关神经生物学的信息，这些信息是从休闲乙醇使用到成瘾的过渡的基础。这些结果将提供有关特定神经途径在酒精自我管理中的作用的新信息，并增强我们对摄入量的行为机制的理解。因此，这些实验将解决我们对酒精成瘾神经生物学的基本知识的重要缺乏，这将使我们能够更好地设计酗酒的疗法。