The effects of pre-pubertal gonadectomy and binge-like ethanol exposure during adolescence on ethanol drinking in adult male and female rats

The pubertal surge in gonadal hormones that occurs during adolescence may impact the long-term effects of early alcohol exposure and sex differences in drinking behavior in adulthood. We investigated this hypothesis by performing sham or gonadectomy surgeries in Long-Evans rats around post-natal day (P) 20. From P35–45, males and females were given saline or 3.0 g/kg ethanol using a binge-like model of exposure (8 injections total). As adults (P100), they were trained to self-administer ethanol via a sucrose-fading procedure and then given access to different unsweetened concentrations (5–20%, w/v) for 5 days/concentration. We found that during adolescence, ethanol-induced intoxication was similar in males and females that underwent sham surgery. In gonadectomized males and females, however, the level of intoxication was greater following the last injection compared to the first. During adulthood, females drank more sucrose per body weight than males and binge-like exposure to ethanol reduced sucrose consumption in both sexes. These effects were not seen in gonadectomized rats. Ethanol consumption was higher in saline-exposed females compared to males, with gonadectomy reversing this sex difference by increasing consumption in males and decreasing it in females. Exposure to ethanol during adolescence augmented ethanol consumption in both sexes, but this effect was statistically significant only in gonadectomized females. Together, these results support a role for gonadal hormones during puberty in the short- and long-term effects of ethanol on behavior and in the development of sex differences in consummatory behavior during adulthood.

Research highlights▶ Ethanol intoxication after repeated exposure was greater in gonadectomized rats. ▶ In adulthood, females consumed more sucrose and ethanol than males. ▶ These sex differences in consumption were not evident in gonadectomized rats. ▶ Sucrose and ethanol consumption was modulated by ethanol pre-exposure. ▶ The ethanol pre-exposure effect was greatest in gonadectomized females.