Absence of Effects of Intermittent Access to Alcohol on Negative Affective and Anxiety-like Behaviors in Male and Female C57BL/6J Mice

Alcohol use disorder is highly comorbid with other neuropsychiatric disorders such as depression and anxiety. Importantly, women and men are affected differentially by heavy drinking, with women experiencing longer negative affective states after intoxication and increased likelihood to present with comorbid mood or anxiety disorders. In rodents, several studies using different alcohol administration models have shown the development of depressive-like or anxiety-like phenotypes that emerge during abstinence. In this study, we compared the emergence of negative affective behaviors during abstinence from 7 weeks of two-bottle choice intermittent access to 20% alcohol in male and female C57BL/6J mice, a drinking paradigm little studied in this context. Half of the mice were tested 24 hours into abstinence on the elevated zero maze and 19-20 days into abstinence in a novel object in the home cage encounter test. The other half of the mice were tested 27-28 days into abstinence with the novelty-suppressed feeding test. As expected, females drank more than males across the 7 weeks of access to alcohol. Drinking history did not affect performance on these tasks, with the exception of increasing the number of open arm entries on the elevated zero maze. Interestingly, in alcohol-naïve mice, females showed fewer anxiety-like behaviors than males in the elevated zero maze and the novelty-suppressed feeding test. Our results suggest that the intermittent access model does not reliably induce negative affective behaviors on these tasks, and that behavior in female and male mice differs across these tests. Rather, intermittent alcohol drinking may induce a mild form of behavioral disinhibition. Thus, the model of alcohol access is a critical factor in determining the appearance of behavioral disturbances that emerge during abstinence.