Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder

Background: We used positron emission tomography imaging with [¹¹C]raclopride to examine the effects of consumption of alcohol or placebo beverage by participants with alcohol use disorder (AUD) compared with healthy participants with and without family history of AUD. We sought to assess dopamine release following alcohol exposure in relation to AUD risk. Methods: Three groups were enrolled: participants with AUD (n = 15) and healthy participants with family history negative (n = 34) or positive (n = 16) for AUD. Participants consumed a placebo (n = 65) or alcohol (n = 63) beverage in counterbalanced order before positron emission tomography scanning (128 scans). Binding potential (BP_ND) in the two drink conditions and the percent change in BP_ND between conditions were evaluated across striatal subregions. Subjective effects of beverage consumption were rated. Effects of group, drink order, and sex were evaluated. Results: Alcohol resulted in greater dopamine release than did placebo in the ventral striatum (p <.001). There were no main effects of group, drink order, or sex on ventral striatum BP_ND or percent change in BP_ND. However, there was a drink order-by-group interaction (p =.02) whereby family history–positive participants who received placebo first had both lower placebo BP_ND and less difference between placebo and alcohol BP_ND than all other groups, consistent with expectation of alcohol powerfully evoking dopamine release in this group. Subjective responses showed the same order-by-group interaction. Conclusions: Hyper-responsivity of the dopaminergic system in family history–positive participants to expectation of alcohol may contribute to the expression of familial risk for AUD.