Contextual conditioning with amphetamine in humans: Causes and consequences

说明(申请人提供)：毒品效应与周围的人、地点和用具(线索)之间的已知联系是成功治疗毒瘾的主要障碍；尽管努力戒除毒瘾，但这些联系仍然非常持久，即使在长期戒毒后也可能引发对毒品的渴望和复发。因此，药物和药物线索之间的联系构成了一个独特的治疗目标，但几乎没有临床证据表明这种联系是如何形成的，对于线索对药物消费的直接影响的经验支持也有限。这项研究的长期目标是了解药物线索是如何与药物体验紧密联系在一起的，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。这项拟议的研究项目的目的是确定d-苯丙胺与其所在场所之间的联系如何影响娱乐性吸毒者的情绪、行为和对该药物的急性反应。申请者开发了一种新的模型，该模型特别适合于研究有条件的药物关联，因为接触d-苯丙胺和与药物配对的环境可以仔细控制，从而对结果进行全面分析。工作假设是，d-苯丙胺条件化线索(语境)改变了对药物的行为和主观反应，从而影响了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，以抵消对条件药物线索的反应，它们对行为的影响，以及药物消费。这一假设基于申请者实验室的强大初步数据，将通过三个具体目标进行检验：1)在d-苯丙胺和诱导接近该环境的独特环境(即寻求毒品行为)之间建立有条件的联系；2)确定对d-苯丙胺的急性主观反应的个体差异如何影响药物与环境之间的条件联系的发展；以及3)在药物配对的情况下确定对d-苯丙胺的条件情绪和主观反应。我们相信，拟议的研究计划是创新的，因为它将研究d-苯丙胺和环境之间的条件性联系是如何在人类中形成的，以及这些条件性联系对行为、情绪和对药物的急性主观反应的影响。这一研究项目意义重大，因为它将大大促进和扩大我们对药物和线索之间的条件性联系是如何在具有有限药物经验的人类中获得的理解，以及它们对药物寻求和药物奖励的影响。最终，这一知识有望为开发新的策略和药物疗法提供信息，以在有效的治疗方法中抵消对条件线索的反应。

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.