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Weafer J1, Lyon NP1, Gorka SM2, Phan KL2, de Wit H1

1Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, USA
2Department of Psychiatry, University of Illinois at Chicago, Chicago, USA

Individuals with poor inhibitory control are at increased risk for drug and alcohol abuse. There is mounting evidence from both preclinical and clinical studies that poor inhibitory control and reward sensitivity share common neural substrates. Therefore, it is possible that individuals with poor inhibition are at increased risk in part because they experience greater rewarding effects from drugs. Here, we present data from a series of studies with healthy young adults examining neural correlates of response inhibition, as assessed by fMRI during performance of the Stop Signal Task, in relation to sensitivity to both drug and non-drug rewards. First, we report that hypo-frontal activity during response inhibition is associated with sensitivity to the rewarding effects of two drugs of abuse: d-amphetamine (20 mg) and alcohol (0.8 g/kg). In the amphetamine study, low activation in the right inferior frontal gyrus during response inhibition was associated with greater subjective response to amphetamine and greater behavioral preference for amphetamine over placebo. Data collection for the alcohol study is currently underway. In separate analyses with a non-drug reward (sweet taste) we found that hypo-activation in a nearby cluster in the right superior frontal gyrus is associated with greater liking of an intensely sweet taste. Taken together, these findings support the hypothesis that hypo-activation in right frontal brain regions involved in response inhibition is related to heightened sensitivity to both non-drug rewards and drug rewards, including both amphetamine and alcohol. Ultimately, these findings may lead to behavioral and pharmacological interventions that simultaneously improve control and reduce reward sensitivity in impulsive individuals.