Gender differences of acute and chronic administration of dehydroepiandrosterone in rats submitted to the forced swimming test

Previous pre-clinical and clinical studies investigating the antidepressant potential of DHEA revealed conflicting results. In this study, the effects of exogenous DHEA on performance in the forced swimming test (FST) were examined in male and female Wistar rats in different phases of the estrous cycle. Furthermore, the effects of treatment and of the FST, on corticosterone and DHEA serum levels were investigated. Acute administration of DHEA (2 mg/kg) significantly increased freezing only in proestrus female rats. Similarly, the chronic administration of DHEA (2 mg/kg) increased freezing duration and decreased climbing behavior but only in females in diestrus II compared to those given vehicle. These results demonstrate that chronically administered DHEA induces a depressant-like effect, and this effect is sex dependent. There was no direct correlation between corticosterone levels or the corticosterone/DHEA ratio and the behaviors studied. After the FST, serum DHEA and corticosterone levels were increased, with females showing higher DHEA levels than males. Nevertheless, corticosterone levels were unaltered with chronic procedure; an effect that was independent of sex and treatment. These findings are relevant for research examining alternative treatment for depression and may elucidate the gender differences involved in stress-related diseases.