We investigated the actions of the
neuroactive steroid,
pregnanolone [corrected] and the ovarian
steroid, 17beta-estradiol, on seizure expression during two time points of
ethanol withdrawal (EW). Both
steroids can exert rapid, nongenomic actions on the brain that include modulation of seizure activity. Because their basal levels differ in adult males and females and a major symptom of EW is increased seizure risk, we wanted to determine whether these
steroids were
anticonvulsant during EW. Rats were made
ethanol-dependent by administration of 6%
ethanol in a nutritionally complete liquid diet for 14 days. After removal of the
ethanol-containing diet, EW and paired control rats were tested at 1 or 3 days for seizure responses to
pentylenetetrazol. Consistent with previous reports, females seemed to have recovered from EW more quickly than males. We observed significant sex differences in responses to the
steroids, primarily at 3 days EW.
Pregnanolone afforded protection against
seizures with larger effects during EW than in control conditions and greater effects in female than male rats. In contrast, effects of
estradiol were mixed. Some responses of ovariectomized female rats were similar to intact females, whereas other responses were more similar to males. Our behavioral findings are consistent with observed EW-induced changes in plasma
corticosterone levels, showing persistent elevations in male but not female rats. These results support and extend earlier findings suggesting that although the hormonal milieu influences EW, innate differences in brain structure between the sexes also contribute to sex differences in EW.