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

Abstract

Alcohol use disorders (AUDs) are a major problem across the United States. 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 anxiety-like behavior and subsequent EtOH intake, we did find that depressive-like behavior predicted future EtOH intake in females rats only. In addition, we observed an increase in depressive-like behavior is male rats in both the water and EtOH drinking groups. Furthermore, 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. Together, these experiments provide important information on the complex interaction between negative affect and alcohol intake and how these two contexts reciprocally do, or do not, influence each other in a sex-specific manner.

Genetics and epigenetics: paternal adolescent ethanol consumption in serotonin transporter knock-out rats and offspring sensitivity to ethanol

“…Other studies show that female mice and rats acquire ethanol self-administration faster (Melón et al 2013 ; Moore and Lynch 2015 ), show less withdrawal symptoms (Varlinskaya and Spear 2004 ), and have a lower response to pharmacological treatments for AUD (Moore and Lynch 2015 ) compared to males. However, studies have reported greater ethanol consumption in adolescent males (Vetter-O'Hagen et al 2009 ) or have found no sex differences in either adolescent (Lancaster et al 1996 ) or adult (Quadir et al 2022 ) rats. However, Quadir et al ( 2022 ) did find sex-dependent interactions of affective states with ethanol intake and how the two may influence each other.…”

“…However, studies have reported greater ethanol consumption in adolescent males (Vetter-O'Hagen et al 2009 ) or have found no sex differences in either adolescent (Lancaster et al 1996 ) or adult (Quadir et al 2022 ) rats. However, Quadir et al ( 2022 ) did find sex-dependent interactions of affective states with ethanol intake and how the two may influence each other. The enhanced rewarding effects in females are also apparent in conditioned place preference studies, where adult females show a clear preference for ethanol, while males do not (Torres et al 2013 ).…”

Chronic Alcohol Drinking Drives Sex-Specific Differences in Affective Behavior and Medial Prefrontal Cortex Activity in CRF1:Cre:Tdtomato Transgenic Rats

“…However, affective tests are rarely repeated in the same subjects; thus, there are limited findings regarding the effects of time and re-testing on behavior. In one study, researchers found that male rats, but not female rats, spent significantly less time grooming on the second splash test 70 . While the current findings indicate decreased motivation regardless of sex, strain differences may account for this discrepancy.…”

Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system

“…Splash testing was conducted in the modified home cage based on procedures from Quadir and colleagues 37 . After 2 min acclimation, mice were exposed to a spray of sucrose (10% w/v; in DI water), delivered from an atomizer (100 uL) to the dorsal coat.…”