How do conditioned alcohol associations promote alcohol drinking

描述（由申请人提供）：酒精与饮酒周围的人、地点和物品（线索）之间的学习联系是成功治疗酒精依赖的主要障碍；这些联系是非常持久的，尽管努力消除它们，并且可以引发酒精渴望和复发，即使在长时间的戒酒后。因此，酒精和酒精线索之间的联系构成了一个独特的治疗目标，但很少有临床证据表明这种联系是如何形成的，而且线索对酒精消费的直接影响的经验支持有限。这项研究的长期目标是了解酒精线索是如何与饮酒紧密联系起来的，它们对生理和行为的影响，以及它们是如何促进酒精消费和酒精依赖的。拟议的研究项目的目的是确定酒精和饮酒地点之间的联系如何影响即兴饮酒，以及在重度饮酒者中使用从头调节模型的因果关系背后的行为过程。这种在申请人实验室开发的新模型特别适合于研究条件酒精关联，因为暴露于酒精和酒精配对的环境中可以仔细控制，从而可以对结果进行全面分析。目前的假设是，酒精条件提示（情境）改变了对酒精的行为和主观反应，从而调节了饮酒量的增加。该项目的基本原理是，关于酒精环境条件反应的重要知识将导致新的策略来抵消对条件酒精线索的反应，它们对行为和饮酒的影响。该假设基于来自申请人实验室的强有力的初步数据，将通过三个具体目标进行测试：1)识别酒精配对情境下对酒精的情绪、行为和主观反应；2)评估酒精配对情境下的即兴饮酒，并确定其与酒精的情绪、行为和主观反应的关系；3)确定酒精主观反应的个体差异如何影响酒精与情境之间条件关联的发展。我们认为，拟议的研究计划是创新的，因为它将研究酒精和环境之间的条件关联是如何在人类中形成的，条件关联对情绪和行为的影响，以及它们对酒精消费的直接影响。这个研究项目意义重大，因为它将推进和扩大对酒精和线索之间的条件关联是如何获得的，以及它们对酒精奖励、欲望和消费的影响的理解。最终，这些知识有望为新策略和药物治疗的发展提供信息，以在有效的治疗方法中抵消对条件提示的反应。

DESCRIPTION (provided by applicant): Learned associations between alcohol and the people, places and paraphernalia (cues) surrounding alcohol drinking represent a major barrier to the successful treatment of alcohol dependence; these associations are remarkably persistent, despite efforts to extinguish them, and can trigger alcohol craving and relapse even after long periods of abstinence. Thus, associations between alcohol and alcohol cues constitute a unique target for treatment but there is little clinical evidence of how the associations are formed, and limited empirical support for a direct effect of cues on alcohol consumption. The long-term goal of this research is to understand how alcohol cues become powerfully linked with alcohol drinking, their influences on physiology and behavior, and how they promote alcohol consumption and alcohol dependence. The objective of the proposed research project is to determine how associations between alcohol and the places where it is consumed influence ad lib drinking and the behavioral processes underlying the causal link using a de novo conditioning model in heavy drinkers. This novel model, developed in the applicants' laboratory, is particularly well-suited to studying conditioned alcohol associations because exposure to alcohol and alcohol-paired environments can be carefully controlled allowing a comprehensive analysis of the results. The working hypothesis is that alcohol conditioned cues (contexts) alter behavior and subjective responses to alcohol which mediate an increase in drinking. The rationale for the project is that vital knowledge regarding conditioned responses to alcohol contexts will lead to novel strategies to counteract responses to conditioned alcohol cues, their influence on behavior, and alcohol drinking. The hypothesis, based upon strong preliminary data from the applicants' laboratory, will be tested by three specific aims: 1) Identify mood, behavior and subjective responses to alcohol in the alcohol-paired context, 2) Assess ad lib alcohol drinking in the alcohol-paired context and determine how it is related to mood, behavior and subjective responses to alcohol, and 3) Determine how individual differences in alcohol subjective response influence the development of conditioned associations between alcohol and contexts. We believe that the proposed plan of research is innovative because it will examine how conditioned associations between alcohol and contexts are formed in humans, the influence of the conditioned associations on mood and behavior, and their direct effect on alcohol consumption. This research project is significant because it will advance and expand understanding of how conditioned associations between alcohol and cues are acquired and of their influences on alcohol reward, wanting and consumption. Ultimately this knowledge is expected to inform the development of novel strategies and pharmacotherapies to counteract responses to the conditioned cues in effective treatment approaches.