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侧重于对酒精的生物行为反应，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积极强化(即，为了感觉良好而饮酒)向消极强化(即，为了不感到不舒服或为了感觉正常)的过渡，代表了一个进行性神经生物学失调的循环。人体实验室中的酒精给药研究允许通过检查不同饮酒水平(即酗酒或酒精依赖组)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。到目前为止，还没有研究使用酒精给药范例将酒精中毒病因学的神经生物学模型转换到临床人群中。这一应用的目的是在人体实验室中检验酒精中毒病因学的成熟的神经生物学理论。为了做到这一点，本研究结合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。为了模拟从积极饮酒到消极饮酒的转变，将招募两组(n总计=82)，a 一组不依赖大量饮酒的人和一组依赖酒精的个人。一个探索性的目的是研究酒精积极和消极强化作用的候选基因。这项拟议的研究通过测试神经生物学假设来扩展酒精中毒文献，这些假设涉及饮酒状态对实验室中对酒精的主观反应的调节作用，以及主观反应与随意服用额外酒精的自我管理之间的关系。

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.