Sex differences in striatal dopamine release in young adults after oral alcohol challenge: a positron emission tomography imaging study with [¹¹C]raclopride.
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.
Urban
Nina B L
NB
Department of Psychiatry at New York State Psychiatric Institute and Columbia University, New York, New York 10032, USA. nu2118@columbia.edu
Kegeles
Lawrence S
LS
Slifstein
Mark
M
Xu
Xiaoyan
X
Martinez
Diana
D
Sakr
Ehab
E
Castillo
Felipe
F
Moadel
Tiffany
T
O'Malley
Stephanie S
SS
Krystal
John H
JH
Abi-Dargham
Anissa
A
D000328:Adult; D000428:Alcohol Drinking / Q000097:blood / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D012727:Sex Characteristics
D002250:Carbon Radioisotopes; D020891:Raclopride; D004298:Dopamine