Medial orbitofrontal cortex dysfunction in alcohol dependence assessed by using a dextroamphetamine probe and functional magnetic resonance imaging

Abstract

A loss of prefrontal modulation of dopamine cell activity in the ventral striatum has been reported in alcohol dependence with a suggested orbitofrontal cortex involvement. Alcohol-cue exposure paradigms have been used in functional neuroimaging studies of alcohol dependence using validated alcohol cues that have shown to activate specific mesocorticolimbic dopamine system areas such as the ventral striatum and the orbitofrontal cortex. Our objective was to assess how these mesocorticolimbic brain areas responded to a dopamine challenge in alcohol-dependent participants exposed to alcohol cues. In a single-blind, between-subject study, 14 non-abstinent alcohol-dependent participants and 9 controls (social drinkers) were administered a single oral dose of dextroamphetamine (30 mg). Functional magnetic resonance imaging blood oxygen level–dependent activation was measured during an alcohol-cue exposure task pre- and post-drug. Alcohol-dependent participants exhibited greater ventral striatal activation compared to controls pre-drug and post-drug effect (F_1,40=20.1; z=3.8; p<0.001; k>10; (x=10;y=-2;z=-14)). A GROUPxDRUG interaction effect was detected in the medial orbitofrontal cortex (mOFC) (F_1,40=21.5; z=4.0; p<0.001; k>10; (x=-12;y=28;z=-20). The alcohol-dependent group exhibited a negligible mOFC response across both pre- and post-drug scanning sessions. In contrast, controls exhibited attenuation of mOFC response post-drug. These results suggest there may be ventral striatal and medial orbitofrontal cortex disruption in alcohol-dependent participants. The medial orbitofrontal cortex may be a key area responsible for the loss of prefrontal modulation of ventral striatal dopamine cell activity in alcohol dependence. Further research on medial orbitofrontal cortex dysfunction in alcohol dependence is warranted and may lead to future treatment targets.