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: 8702577
• 负责人: EMMA CHILDS
• 金额: $ 2.09万
• 依托单位: UNIVERSITY OF 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 2014-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702577
• 关键词: Abstinence; Acute; Alcohol consumption; Alcohols; Amphetamines; Animals; Association Learning; Behavior; Behavior Control; Characteristics; Clinical; Communities; Consumption; Cues; Data; Development; Dextroamphetamine; Drug Addiction; Drug abuse; Drug user; Ensure; Environment; Exhibits; Exposure to; Goals; Health; Human; Human Volunteers; Incentives; Individual; Individual Differences; Knowledge; Laboratories; Lead; Link; Methodology; Methods; Mission; Modeling; Moods; National Institute of Drug Abuse; Pharmaceutical Preparations; Pharmacotherapy; Physiology; Pilot Projects; Placebos; Prevention; Public Health; Recreational Drugs; Relapse; Reporting; Research; Research Project Grants; Rewards; Stimulus; Testing; Time; Work; addiction; animal data; approach behavior; base; behavior measurement; conditioning; drinking; drug craving; drug efficacy; drug relapse; drug reward; drug seeking behavior; effective therapy; experience; improved; innovation; interest; novel; novel strategies; preference; prevent; psychostimulant; research study; response; theories; treatment strategy

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）：毒品作用与围绕药物体验的人，地点和用具（提示）之间的学识渊博的关联是成功治疗药物成瘾的主要障碍；尽管努力扑灭它们，但即使经过长时间的禁欲，这些关联仍然非常持久，并且可以引发毒品的渴望和复发。因此，药物与药物提示之间的关联构成了治疗的独特目标，但是几乎没有临床证据表明如何形成关联，并且有限的经验支持对提示对药物消耗的直接影响。这项研究的长期目标是了解药物线索如何与药物体验，对生理学和行为的影响以及它们如何促进药物消费和成瘾有效地联系在一起。拟议的研究项目的目的是确定D-苯丙胺与经历的地方之间的关联如何影响娱乐吸毒者对药物的情绪，行为和急性反应。申请人开发了一种新型模型，该模型特别适合研究条件药物关联，因为可以仔细控制对D-苯丙胺和药物对环境的暴露，从而可以全面地分析结果。工作假设是D-苯丙胺条件提示（上下文）改变了对药物的行为和主观反应，从而影响了药物的整体奖励疗效。该项目的理由是，关于对药物配对环境的条件反应的重要知识将导致应对对条件药物提示的反应，对行为的影响和药物消耗的新策略。该假设基于申请人实验室的强大初步数据，将通过三个具体目的测试：1）建立D-苯丙胺与独特的环境之间建立条件关联，这些环境诱导了该环境的方法在药物配对的情况下对D-苯丙胺的反应。我们认为，拟议的研究计划具有创新性，因为它将研究在人类中如何形成d-苯丙胺与环境之间的条件关联，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。该研究项目之所以重要，是因为它将大大提高并扩展我们对毒品和提示之间的条件关联的理解，这些人与药物经验有限的人类以及对药物寻求药物和药物奖励的影响。最终，这种知识有望为新型策略和药物治疗的发展提供信息，以抵消有效治疗方法中对条件线索的反应。