The Neural Bases of Affect Regulation in Drug Abuse

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.