Subjective Response and Self-Administration of Alcohol in the Human Lab

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酒精中毒病因的神经生物学模型的临床人群。这个NRSA应用程序的目的是通过在人类实验室中调查酒精中毒病因学的成熟神经生物学理论，促进我作为临床神经科学家的发展。要做到这一点，本研究结合传统的酒精挑战和渐进的比例自我管理的方法来阐明主观反应酒精和一个人的意愿工作酒精之间的关系。为了模拟从积极到消极的强化酒精使用的过渡，将招募两组（ntotal = 82），一组非依赖性重度饮酒者和一组酒精依赖个体。本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的调节作用，在实验室中的主观反应酒精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 NRSA application is to foster my development as a clinical neuroscientist focusing on alcoholism through the investigation of 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 (ntotal = 82) will be recruited, a group of non-dependent heavy drinkers and a group of alcohol dependent individuals. The present 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.