Sex differences in alcohol consumption and behavioral responses after the interruption of chronic ethanol drinking plus a single intraperitoneal administration

Alcohol exposure can differentially affect males and females, with sex-related differences in alcohol consumption and behavioral responses. We investigated alcohol consumption and behavioral responses in a model of chronic ethanol consumption plus a single ethanol injection in both sexes. Adult C57BL/6 mice received a liquid diet containing ethanol (5% v/v) for 10 days, followed by ethanol injection (2.5 g/kg, i.p.) on day 11. Alcohol consumption was calculated per cage and expressed as g/kg body weight. Behavioral responses were evaluated using the Open Field Test (OFT) after 24 h of withdrawal and contextual fear conditioning on day 4 of withdrawal. Females showed higher alcohol consumption than males during the last three days of the diet protocol. In the OFT, females showed greater total locomotor activity than males under both control and ethanol-exposed conditions, with a strong tendency toward a sex difference in time spent in the central zone under control conditions. Ethanol-exposed males showed reduced time spent in the central zone and total locomotor activity. In fear conditioning, males showed a trend toward higher freezing than females under control conditions, whereas this difference was significant after ethanol exposure. Ethanol exposure increased freezing in both sexes. Overall, these findings reveal sex-related differences in alcohol consumption and behavioral responses following chronic ethanol exposure and an acute ethanol challenge, highlighting the im