The Neural Bases of Affect Regulation in Drug Abuse

描述（由申请人提供）：尽管行为和神经生物学证据表明，甲基苯丙胺（MA）滥用者和药物滥用者普遍表现出较差的自我控制能力，但很少有研究直接研究滥用者利用基本社会认知行为研究中显示的认知重评价，来“冷却”由与药物相关的食欲刺激产生的“热”冲动的能力，这种能力在延迟或放弃诱人奖励的消费方面非常有效。本研究探讨了应用这些认知评估策略的效用，以确定在哪些条件下，MA滥用者可以a)使用重新评估策略来“冷却”药物刺激的“热”食欲，b)招募支持这些重新评估的前额叶和扣带机制，以及c)作为结果，减少对“热”药物的感知欲望和杏仁核等结构的激活，这些结构可能有助于他们的冲动食欲反应。为了实现这些目标，我们将分两步追求两个目标。首先，我们将建立一个支持重新评估健康年轻人食欲冲动的神经基础的规范模型。其次，在Aim 1下开发的情感调节的规范模型将用于识别介导MA使用障碍易感性的认知和神经过程。具体来说，在资助的第1-2年，我们将对健康成人进行2项实验，研究对可能引发对渴望的食欲物体的渴望（实验1）的图像刺激的“加热”和“冷却”评价的神经基础，或在没有外部线索的情况下可能引发情感冲动的食欲经历的记忆（实验2）。在资助的第3-5年，我们将使用这些范式来研究MA滥用者样本的重新评估，这些滥用者已经完成了正在进行的NIDA资助的鼻内MA自我给药研究（R01 DA019559）。这项研究仔细地描述了MA使用和反应的模式，使我们能够将MA滥用者的吸毒行为与我们将在本提案中获得的关于他们使用认知重新评估和支持他们重新评估工作的神经机制的发现联系起来。该研究直接探讨了药物依赖的社会认知机制和神经机制，以确定它们如何相互作用，试图使用认知评估策略来降低MA的吸引力和力量，MA是一种非法使用急剧增加的药物。

DESCRIPTION (provided by applicant): Although behavioral and neurobiological evidence suggests that methamphetamine (MA) abusers and drug abusers more generally exhibit poor self-control, little work has directly examined the ability of abusers to "cool" the "hot" impulses generated by appetitive drug-related stimuli using the kinds of cognitive reappraisals shown in basic social cognitive behavioral work to be highly effective for delaying or foregoing consumption of attractive, tempting rewards. This proposal examines the utility of applying these cognitive appraisal strategies to identify the conditions under which MA abusers can a) use reappraisal strategies to "cool" the "hot" appetitive pull of drug stimuli, b) recruit the prefrontal and cingulate mechanisms supporting these reappraisals, and c) as a consequence, reduce the perceived desirability of the "hot" drug and activation in structures like the amygdala that may contribute to their impulsive appetitive responses. Toward these goals, we will pursue 2 aims in 2 steps. First, we will develop a normative model of the neural bases supporting reappraisal of appetitive impulses in healthy young adults. Second, the normative model of affect regulation developed under Aim 1 will be used to identify the cognitive and neural processes that mediate vulnerability to MA use disorders. Specifically, in years 1-2 of the grant, in 2 experiments with healthy adults we will examine the neural bases of "heating" and "cooling" appraisals of pictorial stimuli of the sort that may elicit cravings for desired appetitive objects (Exp 1), or memories of appetitive experiences that may trigger affective impulses in the absence of external cues (Exp 2). In years 3-5 of the grant, we will use these paradigms to study reappraisal in a sample of MA abusers who have completed participation in an on- going NIDA funded study (R01 DA019559) of intranasal MA self-administration. This study carefully characterizes patterns of MA use and response, allowing us to relate the drug-taking behaviors of MA abusers to the findings we will obtain in this proposal concerning their use of cognitive reappraisals and the neural mechanisms supporting their reappraisal efforts. The proposed research directly addresses both the social-cognitive mechanisms and the neural mechanisms basic in drug dependency, to identify how they interact in attempts to use cognitive appraisal strategies to reduce the attractiveness and power of MA, a drug whose illicit use is increasing dramatically.