Acquisition and persistence of drug cue conditioning in humans - Resubmission 01

人类药物线索调节的获取和持久性 - 重新提交 01

• 批准号: 9389315
• 负责人: HARRIET DE WIT
• 金额: $ 9.75万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9389315
• 关键词: Adult; Alcohols; Animal Model; Animals; Attention; Auditory; Behavior; Behavioral; Brain; Brain region; Clinical; Cognitive; Collaborations; Conditioned Reflex; Conditioned Stimulus; Corpus striatum structure; Cues; Dependence; Desire for food; Development; Dose; Drug usage; Drug user; Electromyography; Emotional; Extinction (Psychology); Functional Magnetic Resonance Imaging; Future; Goals; Human; Illicit Drugs; Incentives; Individual Differences; Intramural Research Program; Knowledge; Laboratories; Laboratory Animal Models; Laboratory Animals; Learning; Link; Literature; Measures; Methamphetamine; Methods; Motivation; National Institute on Alcohol Abuse and Alcoholism; Outcome Measure; Pattern; Pharmaceutical Preparations; Physiological; Physiology; Play; Population; Procedures; Process; Property; Psychophysiology; Relapse; Rewards; Role; Signal Transduction; Stimulus; Testing; Time; Visual; addiction; attentional bias; auditory stimulus; behavior measurement; classical conditioning; conditioning; craving; cue reactivity; drug seeking behavior; experience; healthy volunteer; improved; motivated behavior; novel; paired stimuli; preference; public health relevance; relating to nervous system; response; visual stimulus

DESCRIPTION (provided by applicant): This project will examine the acquisition of conditioned drug-related responses in healthy adults. Conditioned drug cues are believe to play an important role in drug use, especially in relapse when they illicit drug-seeking behavior. Although numerous studies have demonstrated acquisition of conditioned drug cues in animal models, few studies have examined acquisition and expression of these responses in humans. To understand how conditioned stimuli acquire their powerful motivational force, we need to understand how they are acquired, how the conditioned responses are manifested (e.g., behavioral, physiological, neural), and how they persist. The knowledge gained will provide a translational link between the rich animal literature and the human clinical situation, and eventually allow us to target the learned responses as targets for addiction treatment. We have developed a novel procedure to study acquisition of Pavlovian conditioned responses in humans, showing that visual and auditory stimuli paired with a moderate dose of methamphetamine acquire positive incentive properties. Here, we propose to refine the procedure. We will measure the responses using sensitive measures of behavior, physiology, and brain activity using fMRI. We will determine the optimal parameters of conditioning, test the persistence and extinction of the conditioned response, and test the effects of the stimulus on emotional responses and neural activity using fMRI. Together, these studies will improve our understanding of how conditioning contributes to drug use, and provide a strong method and empirical basis to study conditioning with other drugs, the effects of potential treatment medications, and individual differences in cue reactivity.

描述（由申请人提供）：本项目将检查健康成人条件性药物相关反应的获得。条件性药物线索被认为在药物使用中起着重要作用，特别是在他们非法寻求药物行为的复吸中。尽管许多研究已经证明了动物模型中条件性药物线索的获得，但很少有研究人类这些反应的获得和表达。为了理解条件刺激是如何获得其强大的动机力量的，我们需要了解它们是如何获得的，条件反应是如何表现的（例如，行为的、生理的、神经的），以及它们如何持续。所获得的知识将在丰富的动物文献和人类临床情况之间提供翻译联系，并最终使我们能够将学习反应作为成瘾治疗的目标。我们已经开发了一种新的程序来研究人类巴甫洛夫条件反射的获得，表明视觉和听觉刺激与中等剂量的甲基苯丙胺配对获得积极的激励特性。在此，我们建议改进程序。我们将使用fMRI对行为、生理和大脑活动进行敏感测量。我们将确定条件反射的最佳参数，测试条件反射的持续性和消退，并使用功能磁共振成像测试刺激对情绪反应和神经活动的影响。总之，这些研究将提高我们对条件反射如何促进药物使用的理解，并为研究条件反射与其他药物、潜在治疗药物的影响以及线索反应性的个体差异提供强有力的方法和经验基础。