Sex Differences in Striatal Dopamine Release in Healthy Adults

Background: Sex differences in addictive disorders have been described. Preclinical studies have implicated the striatal dopamine system in these differences, but human studies have yet to substantiate these findings. Methods: Using positron emission tomography (PET) scans with high-specific-activity [¹¹C] raclopride and a reference tissue approach, we compared baseline striatal dopamine binding potential (BP) and dopamine release in men and women following amphetamine and placebo challenges. Subjective drug effects and plasma cortisol and growth hormone responses were also examined. Results: Although there was no sex difference in baseline BP, men had markedly greater dopamine release than women in the ventral striatum. Secondary analyses indicated that men also had greater dopamine release in three of four additional striatal regions. Paralleling the PET findings, men's ratings of the positive effects of amphetamine were greater than women's. We found no sex difference in neuroendocrine hormone responses. Conclusions: We report for the first time a sex difference in dopamine release in humans. The robust dopamine release in men could account for increased vulnerability to stimulant use disorders and methamphetamine toxicity. Our findings indicate that future studies should control for sex and may have implications for the interpretation of sex differences in other illnesses involving the striatum.