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

基本信息

批准号：
9095269
负责人：
HARRIET DE WIT
金额：
$ 43.41万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9095269
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 Development Dose Drug usage Drug user Electromyography Emotional Extinction (Psychology)Functional Magnetic Resonance Imaging Future Goals Health Human Illicit Drugs Incentives Individual Differences Intramural Research Program Knowledge Laboratories Laboratory Animal Models Laboratory Animals Learning Link Literature Measures Methamphetamine Methods 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 Staging Stimulus Testing Time Visual addiction attentional bias auditory stimulus base behavior measurement classical conditioning conditioning craving cue reactivity drug seeking behavior experience healthy volunteer improved motivated behavior novel paired stimuli preference relating to nervous system response visual stimulus

项目摘要

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）：该项目将检查健康成年人中与药物相关的反应的获取。有条件的药物提示被认为在毒品使用中起着重要作用，尤其是当它们非法寻求毒品行为时。尽管许多研究表明在动物模型中获得了条件药物提示的获取，但很少有研究检查了人类这些反应的获取和表达。要了解条件刺激如何获得强大的动力，我们需要了解如何获得它们，如何表现条件反应（例如行为，生理，神经）以及它们如何持久。获得的知识将提供丰富的动物文献与人类临床状况之间的翻译联系，并最终使我们能够以学习的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中帕夫洛维亚条件反应的采集，这表明视觉和听觉刺激与中等剂量的甲基苯丙胺配对具有阳性激励性能。在这里，我们建议完善程序。我们将使用fMRI的行为，生理和大脑活动的敏感度量来衡量反应。我们将确定调理的最佳参数，测试条件反应的持久性和灭绝，并使用fMRI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调节方式如何促进药物使用的理解，并提供强大的方法和经验基础来研究其他药物的调节，潜在治疗药物的影响以及提示反应性的个体差异。