The Neural Bases of Affect Regulation in Drug Abuse

描述（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）滥用者和药物滥用者更普遍地表现出自我控制能力差，很少有工作直接研究滥用者“冷却”食欲药物产生的“热”冲动的能力，相关的刺激，使用在基本的社会认知行为工作中显示的认知重新评估的种类，对于延迟或放弃是非常有效的。有吸引力的，诱人的奖励。本提案考察了应用这些认知评价策略的效用，以确定MA滥用者可以a）使用重新评价策略来“冷却”药物刺激的“热”食欲拉动的条件，B）招募支持这些重新评价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，并激活杏仁核等结构，这可能有助于他们的冲动食欲反应。为了实现这些目标，我们将在两个步骤中实现两个目标。首先，我们将建立一个支持健康年轻人食欲冲动重新评价的神经基础的规范模型。第二，规范性模型的目标1下开发的影响调节将被用来确定的认知和神经过程，介导的脆弱性MA使用障碍。具体来说，在第1-2年的补助金，在2个实验与健康的成年人，我们将检查的神经基础的“加热”和“冷却”的评价的图片刺激的排序，可能会引起渴望所需的食欲对象（实验1），或记忆的食欲经验，可能会触发情感冲动的情况下，外部线索（实验2）。在补助金的第3-5年，我们将使用这些范例研究MA滥用者样本的重新评估，这些滥用者已完成参与正在进行的NIDA资助的鼻内MA自我给药研究（R 01 DA 019559）。本研究仔细的MA使用和响应的模式的特点，使我们能够与MA滥用者的吸毒行为，我们将在这个建议中获得的结果，关于他们使用的认知重新评价和神经机制支持他们的重新评价的努力。拟议的研究直接解决了社会认知机制和药物依赖的神经机制，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的吸引力和力量，这种药物的非法使用正在急剧增加。

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.