Lack of consistent sex differences in D-amphetamine-induced dopamine release measured with [¹⁸F]fallypride PET

Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed.

Here, we sought to investigate sex differences in dopamine release after oral D-amphetamine administration.

We used [¹⁸F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBP_ND, an index of dopamine release) between placebo and D-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males.

Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in D-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control.

While our finding in young adults from one dataset of greater %ΔBP_ND in males is partially consistent with a previously published study on sex differences in D-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.