Modeling alcohol reward and reinforcement in the human laboratory

描述（由申请人提供）：酒精中毒病因学的动物和人类模型都集中在对酒精的生物行为反应上，作为酒精中毒风险脆弱性和疾病进展的潜在标志。在神经生物学模型中，酒精中毒被概念化为从正强化（即，“为了感觉良好而喝酒”）到负强化（即，“喝酒不是为了感觉不好或感觉正常”），代表了一个进行性神经生物学失调的循环。在人体实验室中进行的酒精给药研究通过检查不同饮酒状态水平（即重度饮酒或酒精依赖组）下对酒精的主观反应（包括刺激、镇静和缓解紧张维度），将临床前理论转化为临床人群。到目前为止，没有研究使用酒精管理范式翻译神经生物学模型的酒精中毒病因的临床人群。本申请的目的是在人类实验室研究酒精中毒病因学的成熟神经生物学理论。要做到这一点，本研究结合了传统的酒精挑战和渐进的比例自我管理的方法，以阐明主观反应酒精和一个人的意愿，为酒精工作之间的关系。为了模拟从积极到消极强化酒精使用的过渡，将招募两组（n总计= 82）， 一组非依赖性重度饮酒者和一组酒精依赖者。一个探索性的目标将检查候选基因subserving积极和消极的酒精强化效果。拟议的研究扩展了酒精中毒文献，通过测试神经生物学知情的假设，饮酒状态对主观反应酒精在实验室中的调节作用和主观反应和自我管理额外的酒精自由之间的关系。

DESCRIPTION (provided by applicant): Both animal and human models of alcoholism etiology have focused on biobehavioral response to alcohol as a potential marker of alcoholism risk vulnerability and disease progression. Alcoholism has been conceptualized in neurobiological models as a transition from positive reinforcement (i.e., "drinking to feel good") to negative reinforcement (i.e., "drinking not to feel bad or to feel normal"), representing a cycl of progressive neurobiological dysregulation. Alcohol administration studies in the human laboratory allow for the translation of preclinical theory to clinical populations through examination of the subjective response to alcohol (comprising stimulation, sedation and tension relieving dimensions) at different levels of drinking status (i.e. heavy drinking or alcohol dependent groups). To date, no studies have used alcohol administration paradigms to translate neurobiological models of alcoholism etiology to clinical populations. The objective of this application is to examine well-established neurobiological theories of alcoholism etiology in the human laboratory. To do so this study combines traditional alcohol challenge and progressive ratio self-administration methodologies to elucidate the relationship between subjective response to alcohol and one's willingness to work for alcohol. In order to model the transition from positively to negatively reinforced alcohol use two groups (n total = 82) will be recruited, a group of non- dependent heavy drinkers and a group of alcohol dependent individuals. An exploratory aim will examine candidate genes subserving the positive and negative reinforcing effects of alcohol. The proposed study extends the alcoholism literature through testing neurobiologically informed hypotheses about the moderating role of drinking status on subjective response to alcohol in the lab and the relationship between subjective response and self-administration of additional alcohol ad lib.