The Neural Bases of Affect Regulation in Drug Abuse

描述(由申请人提供)：虽然行为和神经生物学证据表明，甲基苯丙胺(MA)滥用者和吸毒者通常表现出较差的自我控制能力，但很少有研究直接检验滥用者使用基本社会认知行为测试中显示的认知重新评估类型，对延迟或放弃对诱人、诱人的奖励的消费非常有效的能力，来“冷却”与毒品有关的食欲刺激产生的“热”冲动的能力。这项建议考察了应用这些认知评估策略来确定MA滥用者a)使用重新评估策略来“冷却”药物刺激的“热”欲望拉动，b)招募支持这些重新评估的前额叶和扣带回机制，以及c)因此，减少对“热”药物的感知欲望以及杏仁核等结构中可能导致冲动食欲反应的激活的情况下的效用。为了实现这些目标，我们将分两步实现两个目标。首先，我们将开发一个支持重新评估健康年轻人的食欲冲动的神经基础的标准化模型。其次，在目标1下开发的情感调节的标准模型将被用来识别调节易受MA使用障碍影响的认知和神经过程。具体地说，在拨款的第一年到第二年，我们将在两个健康成年人的实验中检查对可能引起对所需欲望对象的渴望的图片刺激的“热”和“冷”评估的神经基础(实验1)，或者在没有外部线索的情况下对可能引发情感冲动的欲望体验的记忆(实验2)。在拨款的第3至第5年，我们将使用这些范例对已完成NIDA资助的正在进行的鼻内MA自我管理研究(R01 DA019559)的MA滥用者进行重新评估。这项研究仔细描述了MA的使用和反应模式，使我们能够将MA滥用者的吸毒行为与我们在本提案中获得的关于他们使用认知重新评估的发现以及支持他们重新评估努力的神经机制联系起来。拟议的研究直接涉及药物依赖的社会认知机制和基本的神经机制，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的吸引力和威力，MA是一种非法使用正在急剧增加的药物。

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.