Evaluation of estradiol administration on the discriminative-stimulus and subject-rated effects of d-amphetamine in healthy pre-menopausal women.

Accumulating evidence suggests that estradiol might be responsible for the enhanced response to psychostimulants sometimes observed in females. In this study, 10 healthy pre-menopausal women who were using oral, hormone-based birth control learned to discriminate 15 mg/70 kg oral d-amphetamine from placebo. Once a discrimination criterion was met (i.e., >or=80% correct responding at the final time point for five consecutive sessions), a range of doses of oral d-amphetamine (0, 3.125, 7.5 and 15 mg/70 kg) was tested alone and in combination with sublingual estradiol (0 and 0.25 mg). Test sessions were conducted during the oral contraception placebo phase when levels of both estradiol and progesterone were at their lowest. d-Amphetamine functioned as a discriminative stimulus and produced prototypical stimulant effects (e.g., increased positive subject-rated drug effects, elevated cardiovascular measures). Estradiol enhanced the discriminative-stimulus effects of the low dose, but not higher doses of d-amphetamine. Estradiol also enhanced d-amphetamine effects on a subset of self-report ratings (i.e., VAS Like Drug and total score on the Stimulant subscale of the Adjective-Rating Scale). These findings provide limited support for the notion that estradiol increases sensitivity to the psychostimulant effects of drugs such as d-amphetamine.