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Anton & Schacht Component

Clinical Research Component

Effects of Cortical Dopamine Regulation on Drinking, Craving, & Cognitive Control

Principal Investigator: Raymond Anton, M.D.
Co-Principal Investigator: Joseph Schacht, Ph.D.

This project focuses on examining whether increasing dopamine tone in the prefrontal cortex with a medication that inhibits catechol-O-methyltransferase (COMT) activity enhances behavioral inhibition and cognitive control while reducing alcohol craving, drinking, and brain activation to alcohol cues.

The project uses bar-lab procedures along with fMRI imaging and a stop-signal task to assess medication effects on drinking and alcohol cue reactivity in relation to measures of behavioral inhibition. Further, the project will employ a prospective genotyping design to examine the effects of allelic variants of the COMT gene on outcome measures.

The general hypothesis to be tested is that the COMT inhibitor, relative to placebo, will reduce natural and bar-lab drinking, and reduce activation to alcohol cues and during inhibition on the stop-signal task – and these effects will be greatest among individuals carrying the COMT val/val genotype (which confers lower cortical dopamine tone). Additionally, functional connectivity analysis will allow for testing the hypothesis that the COMT inhibitor will decrease corticostriatal connectivity during alcohol cue exposure while increasing corticostriatal connectivity during response inhibition.

The project utilizes advanced neuroimaging, genetics, and a lab-based drinking paradigm previously refined during the last funding period of this alcohol research center grant.