Sex differences in affective states and association with voluntary ethanol intake in Sprague-Dawley rats

Alcohol use disorders (AUDs) are a major problem across the USA. While AUD remains a complex human condition, it is difficult to isolate the directionality of anxiety and ethanol (EtOH) drinking from outside influences. The present study sought to investigate the relationship between affective states and EtOH intake using male and female Sprague-Dawley rats. Using complementary tests of anxiety- and depressive-like behavior, we found sex- and test-specific differences in basal affective behavior such that females displayed enhanced anxiety-like behavior in the splash test and males displayed enhanced anxiety-like behavior in the novelty-suppressed feeding test. Although, there were no sex differences in EtOH intake and no correlation between baseline anxiety-like behavior and subsequent EtOH intake, we did find that depressive-like behavior predicted future EtOH intake in female rats only. In addition, we observed an increase in depressive-like behavior is male rats in both the water and EtOH drinking groups (compared to baseline levels). Furthermore, post-drinking anxiety-like behavior, but not depressive-like behavior predicted subsequent EtOH intake in female rats. Lastly, we found a history of EtOH intake decreased pain thresholds in male and female rats, but increased anxiety-like and depressive-like behavior was associated with decreased thermal sensitivity only in EtOH-drinking males. Together, these experiments provide important information on the complex interaction between negative affect and EtOH intake and how these two contexts reciprocally do, or do not, influence each other in a sex-specific manner.