Neural Effects of Weekly Binge Alcohol: Sex Differences?

In the U.S., 1/6 of adults report binge drinking about 4 times a month. There is also mounting evidence indicating that females may be more vulnerable to the neurotoxic effects of ethanol than males. Using a novel model of weekly binge ethanol exposure, we hypothesized that cellular damage would be greater and detectable earlier in female rats in comparison to male rats. Adult Long-Evans rats were administered 5g/kg ethanol (or an iso-caloric control dose) via intra-gastric gavage once-weekly. Neither BEC (177 mg/dl) nor behavioral intoxication measures differed over time, indicating that tolerance did not occur. Male rats, however, acted more behaviorally intoxicated than females. Brains were collected either 4 or 6 days following the final ethanol dose, and immunohistochemically processed for mature neurons (NeuN), microglia (Iba1), neurogenesis (DCX) and cellular activation (c-Fos). Stereology was used to quantify target cell populations in the hippocampus and medial prefrontal cortex (mPFC). We showed that binge ethanol administration for 11 weeks increases partial activation of microglia in the hippocampus and causes significant dentate gyrus (DG) cell loss despite an increase in neurogenesis in female rats. After 3 and 8 weeks, binge ethanol significantly decreased the number of NeuN+ cells in the DG of male and female rats in comparison to controls. 8 weeks of binge ethanol significantly increased the total number of microglia (Iba1) and the number of partially activated microglia in the hippocampus and mPFC in males and females. Despite no noted behavioral deficits during reversal learning, binged rats had increased cellular activation in the mPFC during testing, indicating decreased neural efficiency. Additionally, 8 weeks of ethanol influenced ultrasonic vocalizations in male rats, however had no effect on female rats. Overall, these results show hippocampal cell loss and an increased inflammatory response in ethanol-vulnerable regions following repeated binge exposures in both male and female rats and showed changes in affect in male rats during behavioral testing.