Contextual conditioning with amphetamine in humans: Causes and consequences

安非他明对人类的情境调节：原因和后果

• 批准号: 8996616
• 负责人: EMMA CHILDS
• 金额: $ 21.88万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8996616
• 关键词: Contextual; conditioning; amphetamine; humans; Causes

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.

描述（由申请人提供）：药物效应与药物体验周围的人物、地点和用具（线索​​）之间的已知关联是成功治疗药物成瘾的主要障碍；尽管我们努力消除这些联系，但这些联系仍然非常持久，并且即使在长期戒毒后也可能引发药物渴望和复发。因此，药物和药物线索之间的关联构成了独特的治疗目标，但几乎没有临床证据表明这些关联是如何形成的，并且线索对药物消耗的直接影响的经验支持也很有限。这项研究的长期目标是了解药物线索如何与药物体验密切相关，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。拟议研究项目的目的是确定 d-安非他明和体验它的地点之间的关联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。申请人开发了一种新模型，该模型特别适合研究条件药物关联，因为可以仔细控制暴露于 d-苯丙胺和药物配对环境，从而可以对结果进行全面分析。工作假设是，d-苯丙胺条件线索（背景）改变对药物的行为和主观反应，从而影响药物的整体奖励功效。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费的影响。该假设以申请人实验室提供的强有力的初步数据为基础，将通过三个具体目标进行检验：1) 在苯丙胺与特定环境之间建立条件关联，从而诱导接近该环境，即寻求药物的行为，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关联的发展，以及 3) 确定对 d-苯丙胺的条件性情绪和主观反应药物配对的背景。我们认为，拟议的研究计划是创新的，因为它将研究 d-苯丙胺与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、情绪和对该药物的急性主观反应的影响。这个研究项目意义重大，因为它将极大地推进和扩大我们对药物和线索之间的条件关联如何在药物经验有限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的理解。最终，这些知识有望为新策略和药物疗法的开发提供信息，以抵消有效治疗方法中对条件线索的反应。