Sex Differences in Striatal Dopamine Release in Young Adults After Oral Alcohol Challenge: A Positron Emission Tomography Imaging Study With [11C]Raclopride

Abstract

Objectives-We used a Positron Emission Tomography (PET) paradigm with the D 2/3 radiotracer [ 11 C]raclopride and an alcohol challenge to examine the magnitude of alcohol induced dopamine release and compare it between young men and women.Methods-Twenty-one non-alcohol dependent young social drinkers completed two PET scans on separate days following ingestion of a juice mix containing either ethanol (0.75 mg/kg body water) or trace ethanol only.The extent of dopamine released after alcohol was estimated by the percent difference in [ 11 C]raclopride binding potential (ΔBP ND ) between days.Results-Alcohol administration significantly displaced [ 11 C]raclopride in all striatal subregions indicating dopamine release, with the largest effect observed in the ventral striatum. Linear mixed model analysis across all striatal subregions of regional ΔBP ND with region of interest as repeated measure showed a highly significant effect of sex (p < 0.001). Ventrostriatal dopamine release in men, but not in women, showed a significant positive correlation to alcohol-induced measures of subjective activation. Furthermore, we found a significant negative correlation between the frequency of maximum alcohol consumption per 24 hours and ventrostriatal ΔBP ND (r=0.739, p=0.009) in men.Conclusions-This study provides definitive evidence that oral alcohol induces dopamine release in non-alcoholic human subjects, and shows sex differences in the magnitude of this effect. The ability of alcohol to stimulate dopamine release may contribute to its rewarding effects and, thereby, to its abuse liability in humans. Our report further suggests several biological mechanisms that may mediate the difference in vulnerability for alcoholism between men and women.

Intravenous Ethanol Increases Dopamine Release in the Ventral Striatum in Humans: PET Study Using Bolus-Plus-Infusion Administration of [11C]raclopride

“…8 However, we found that the self-evaluated intoxication level correlated with baseline BP ND values in the left VST, but there was no association in the right side. This lateralization of the association is in agreement with a recent finding, showing that a peak perceived intoxication score correlated with [ 11 C]raclopride baseline BP ND in the left NAcc.…”

“…As the independent effect of scan order was highly significant (P o 0.001) and the order of conditions in both groups was unbalanced, the order effect might have been one confounding factor. 8 Thus, methodological factors might at least partially explain the discrepancies.…”

“…In addition, psychological effects associated with a placebo depend on the order of ethanol administration. 8 Our study used the B/I method with double quantification. The conditioned effects of alcohol drinking and the effects of alcohol anticipation were eliminated by using intravenous ethanol infusion and by blinding the subjects regarding the timing of ethanol infusion.…”

“…7 A recent study applying oral alcohol administration, found a systematic decrease in [ 11 C]raclopride binding in all striatal subregions, suggesting a quite non-specific DA release in male subjects. 8 The dopaminergic effects of ethanol could not, however, be differentiated from the influence of expectation or sensory effects related to drinking alcohol.…”

Beer Flavor Provokes Striatal Dopamine Release in Male Drinkers: Mediation by Family History of Alcoholism

“…Two previous human RAC PET studies suggest that orally consumed alcoholic drinks provoke ventral striatal DA release (Boileau et al, 2003;Urban et al, 2010). In both, however, the orosensory properties of alcohol could have been detectable in the mixed drink.…”