Sex- and time-dependent effects of alcohol hangover on inhibitory avoidance memory in mice

Alcohol hangover begins as blood alcohol concentration approaches zero and can cause cognitive disturbances for several hours. However, how the timing of learning during hangover and biological sex shape memory remains unclear. We examined the effects of ethanol administered at different intervals before training on inhibitory avoidance memory in male and female mice. Adult CF-1 mice received vehicle or ethanol (1.9 g/kg, i.p.) 9 or 12 h before training. Based on the female response profiles at these time points, an additional female cohort was trained 10.5 h after treatment. Previously presented 12-h experiments also included 3.8 g/kg ethanol. Mice received a 0.3-mA footshock upon entering the dark compartment. Entry latency was recorded during training (TR) and a retention test (TS) 48 h later. At 12 h, the analysis revealed a significant group-by-session interaction in males: animals treated with 1.9 g/kg ethanol showed significantly lower TS latencies than vehicle-treated mice, consistent with impaired retention. In contrast, no significant interaction was detected in females in either the initial or replication experiments. At 9 h, ethanol did not significantly alter retention in females or males. Likewise, the 10.5-h female cohort showed no significant group-by-session interaction. Training latencies were comparable between groups in the experiment showing impairment. The 3.8 g/kg dose produced substantial mortality, especially in males, limiting its interpretation.