Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in atâ risk youth

Abstract

Dopamine receptor concentrations, primarily in the striatum, are hypothesized to contribute to a developmental imbalance between subcortical and prefrontal control systems in emerging adulthood potentially biasing motivation and increasing risky behaviors. Positron emission tomography studies have found significant reductions in striatal dopamine D2 receptors, and blunted amphetamineâ induced dopamine release, in substance users compared with healthy controls. Extant literature is limited and inconsistent concerning vulnerability associated with having a family history of substance abuse (FH+). Some studies have reported familial liability associated with higher dopamine receptor levels, reduced dopamine response to stimulant challenges and decreased response to oral alcohol. However, other reports have failed to find group differences based on family history. We explored the interaction of familial liability and behavioral risk with multiâ modal molecular and neural imaging of the dopaminergic system. Fortyâ four young adult male subjects performed monetary incentive delay tasks during both [11C]raclopride positron emission tomography and functional magnetic resonance imaging scans. FH+ subjects were identified as low (nâ =â 24) or high risk (nâ =â 9) based on early initiation of drunkenness. FH+ highâ risk subjects exhibited heightened striatal dopamine response to monetary reward but did not differ in neural activations compared with FH+ low risk subjects and controls with no familial loading (nâ =â 11). Across all subjects, a negative relationship was found between dopamine release and age of first drunkenness and a positive relationship with neural response to reward receipt. These results suggest that in atâ risk individuals, higher dopamine transmission associated with monetary reward may represent a particularly useful neurobiological phenotype.The mesolimbic dopamine system is hypothesized to play a role in vulnerability to substance use disorders. Using multiâ modal methods (functional magnetic resonance imaging and positron emission tomography), we tested whether young adult male subjects at high risk for substance use disorders based on family history and early drunkenness had differences in response to monetary rewards compared with controls. We found heightened striatal dopamine response in highâ risk male subjects during positron emission tomography. This was further associated with age of first drunkenness, suggesting it may represent a neurobiological risk phenotype.