Sex differences in striatal dopamine release in young adults after oral alcohol challenge: a positron emission tomography imaging study with [¹¹C]raclopride

Abstract

Background: We used a positron emission tomography paradigm with the D2/3 radiotracer [¹¹C]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 nonalcohol-dependent young social drinkers completed two positron emission tomography scans on separate days following ingestion of a juice mix containing either ethanol (.75 mg/kg body water) or trace ethanol only. The extent of dopamine released after alcohol was estimated by the percentage difference in [¹¹C]raclopride binding potential (ΔBP(ND)) between days.

Results: Alcohol administration significantly displaced [¹¹C]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 < .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 = .739, p = .009) in men.

Conclusions: This study provides definitive evidence that oral alcohol induces dopamine release in nonalcoholic 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.

Figure 1

Frequency of M (maximum number of drinks per 24 hours) versus ΔBP_ND in VST. Left panel is in men only, n = 11, rho = 0.73, p = 0.012 (Spearman’s rank order coefficient). Right panel includes all men and 7 women, 3 outlier female subjects with very high frequency of M excluded, n = 18, rho = 0.613, p = 0.007. Ordinal logistic regression with frequency of M as an ordinal dependent variable and ΔBP_ND in VST as continuous independent variable reached significance for men alone (n = 11, χ² = 8.28, p = 0.004) and for the entire cohort (n = 21, χ² = 5.46, p = 0.019) but not for women alone.

Figure 2

Striatal change in [¹¹C]raclopride binding potential maps and subjective activation in response to alcohol Binding potential maps averaged across men (n=11, top) and women (n = 10, bottom) following placebo drink (left) and alcohol drink (right). The MRI images (center) are averaged across all 21 subjects. Images were all non-linearly warped into MNI space in the SPM2 software environment (31). The ROIs on the coronal MRI image (left) are the preDCA, preDPU and VST. The line through the sagittal MRI slice (right) shows the coronal slice level of the other images. The graphs on the right show the correlation between subjective activation at 30 minutes after drink (total score post-alcohol minus total score post-placebo, not adjusted for baseline) and absolute ΔBP_ND. The relationship is stronger for men (top). Note that the absolute value of ΔBP_ND is presented here.