Contextual conditioning with amphetamine in humans: Causes and consequences

描述（由申请人提供）：药物效果与药物体验周围的人、地点和物品（线索）之间的学习关联是成功治疗药物成瘾的主要障碍；这些联系是非常持久的，尽管努力消除它们，并可能引发药物渴望和复发，即使在长时间的戒断。因此，药物和药物线索之间的关联构成了一个独特的治疗目标，但很少有临床证据表明这种关联是如何形成的，并且线索对药物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药物线索如何与药物体验紧密联系在一起，它们对生理和行为的影响，以及它们如何促进药物消费和成瘾。拟议的研究项目的目的是确定d-安非他明与使用地点之间的联系如何影响娱乐性药物使用者的情绪、行为和对药物的急性反应。申请人已经开发了一种新的模型，它特别适合于研究条件药物关联，因为暴露于d-安非他明和药物配对环境可以被仔细控制，从而允许对结果进行全面分析。工作假设是d-安非他明条件提示（环境）改变行为和对药物的主观反应，从而影响药物的总体奖励效果。该项目的基本原理是，关于对药物配对环境的条件反应的重要知识将导致新的策略来抵消对条件药物线索的反应，它们对行为和药物消耗的影响。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)建立d-安非他明与特定环境之间的条件关联，诱发对该环境的接近，即寻求药物的行为；2)确定d-安非他明急性主观反应的个体差异如何影响药物与环境之间条件关联的发展；3)确定药物配对背景下d-安非他明的条件情绪和主观反应。我们认为，拟议的研究计划是创新的，因为它将研究d-安非他明和环境之间的条件关联如何在人类中形成，以及条件关联对行为、情绪和对药物的急性主观反应的影响。这项研究项目意义重大，因为它将大大推进和扩展我们对药物和线索之间的条件关联如何在有限的药物经验中获得的理解，以及它们对药物寻找和药物奖励的影响。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 drug effects and the people, places and paraphernalia (cues) surrounding drug experiences represent a major barrier to the successful treatment of drug addiction; these associations are remarkably persistent, despite efforts to extinguish them, and can trigger drug craving and relapse even after long periods of abstinence. Thus, associations between drugs and drug 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 drug consumption. The long-term goal of this research is to understand how drug cues become powerfully linked with drug experiences, their influences on physiology and behavior, and how they promote drug consumption and addiction. The objective of the proposed research project is to determine how associations between d-amphetamine and the places where it is experienced influence mood, behavior and acute responses to the drug in recreational drug users. The applicants have developed a novel model, which is particularly well-suited to studying conditioned drug associations because exposure to d-amphetamine and the drug-paired environment can be carefully controlled allowing a comprehensive analysis of the results. The working hypothesis is that d-amphetamine conditioned cues (contexts) alter behavior and subjective responses to the drug which influences the overall rewarding efficacy of the drug. The rationale for the project is that vital knowledge regarding conditioned responses to drug-paired contexts will lead to novel strategies to counteract responses to conditioned drug cues, their influence on behavior, and drug consumption. The hypothesis, based upon strong preliminary data from the applicants' laboratory, will be tested by three specific aims: 1) Establish a conditioned association between d- amphetamine and a distinct environment that induces approach to that environment i.e., drug-seeking behavior, 2) Determine how individual differences in acute subjective responses to d-amphetamine influence the development of conditioned associations between the drug and environments, and 3) Identify conditioned mood and subjective responses to d-amphetamine in the drug-paired context. We believe that the proposed plan of research is innovative because it will examine how conditioned associations between d-amphetamine and contexts are formed in humans and the influence of the conditioned associations on behavior, mood and acute subjective responses to the drug. This research project is significant because it will substantiall advance and expand our understanding of how conditioned associations between drugs and cues are acquired in humans with limited drug experiences, and of their influence on drug seeking and drug reward. 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.