Human sex differences in d‐amphetamine self‐administration

Abstract

Women and men may respond differently to the effects of stimulants such as amphetamine and cocaine. In order to assess potential sex differences in the reinforcing effects of d-amphetamine, a retrospective-analysis was conducted on data collected from three studies that employed similar d-amphetamine self-administration procedures and used identical subject-rated drug-effect measures. Data from 10 women and 15 men were included in the analysis. In all studies, participants sampled placebo, low (8-10 mg) or high (16-20 mg) dose oral d-amphetamine. Following sampling sessions, participants worked for capsules containing one eighth of the previously sampled dose on a modified progressive-ratio schedule of reinforcement. We hypothesized that women and men would be differentially sensitive to the reinforcing effects of d-amphetamine. A two-way mixed-model analysis of variance (sex and dose) and planned comparisons were used in the statistical analyses. The low dose of d-amphetamine functioned as a reinforcer in women, but not men, whereas the high dose of d-amphetamine functioned as a reinforcer in men, but not women. Men self-administered significantly more capsules under the high dose condition than women. The results of this study suggest that men are more sensitive to the reinforcing effects of a high dose of d-amphetamine than women. Future research is needed that determines prospectively the reinforcing effects of weight-adjusted doses of d-amphetamine in women and men while controlling for menstrual cycle phase.