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专注于对酒精的生物行为反应，作为酒精中毒风险易感性和疾病进展的潜在标志。在神经生物学模型中，酒精中毒被定义为从正强化（即，“为了感觉良好而喝酒”）到负强化（即，“为了感觉良好而喝酒”）的过渡，代表了一个进行性神经生物学失调的循环。人类实验室的酒精管理研究允许通过检查不同饮酒水平（即重度饮酒或酒精依赖群体）对酒精的主观反应（包括刺激、镇静和缓解紧张的维度），将临床前理论转化为临床人群。迄今为止，还没有研究使用酒精管理范式将酒精中毒病因学的神经生物学模型转化为临床人群。这个NRSA申请的目的是通过在人类实验室中对酒精中毒病因学的成熟神经生物学理论的研究，促进我作为一名专注于酒精中毒的临床神经科学家的发展。为此，本研究结合了传统的酒精挑战和递进比例自我管理方法来阐明对酒精的主观反应与一个人为酒精工作的意愿之间的关系。为了模拟从积极加强到消极加强的酒精使用的转变，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性个体。本研究通过在实验室中测试关于饮酒状态对酒精主观反应的调节作用的神经生物学假设，以及主观反应与自我补充酒精之间的关系，扩展了酒精中毒文献。

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.