Both male and female mice were tested in the present study, but sample size did not allow statistical evaluation of sex as a biological variable. That said, we observed tendencies for sex-based differences in Morris Water Maze and prepulse inhibition performance with female data trending toward a greater deficit. This raises the possibility that females may show enhanced vulnerability to the age-dependent effects of alcohol on cognitive function. However, results also showed a trend for female mice to consume higher doses of alcohol than males, which is consistent with evidence from a wide sample of rodent studies (Becker & Koob, 2016); thus, it will be necessary in future preclinical studies to equate alcohol intake between sexes using between group yoking procedures. In addition, sex-based differences in alcohol pharmacokinetics may account for differential neural or behavioral effects, which complicates direct dose-dependent comparisons. Nevertheless, it is important to note that the impact of alcohol on cognitive (memory) function in older adults is more pronounced in women (Lewis et al., 2019) underscoring the importance of conducting future preclinical work to elucidate neural mechanisms that might contribute to female vulnerability.
