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

描述（由申请人提供）：本项目将研究健康成人条件药物相关反应的获得。条件药物线索被认为在药物使用中起着重要作用，特别是当他们非法寻求药物行为时复发。尽管许多研究已经证明了动物模型中条件药物线索的获得，但很少有研究检查了这些反应在人类中的获得和表达。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出来的（例如，行为的，生理的，神经的），以及它们是如何持续的。所获得的知识将提供丰富的动物文献和人类临床情况之间的翻译联系，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应的习得，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，我们建议改进这一程序。我们将使用功能磁共振成像对行为、生理和大脑活动的敏感测量来测量反应。我们将确定条件反射的最佳参数，测试条件反应的持续和消失，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影响药物使用的理解，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的个体差异提供强有力的方法和经验基础。

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.