Sex Differences in Binge-Like and Aversion-Resistant Alcohol Drinking in C57BL/6J Mice

Alcohol use disorder is characterized by compulsive alcohol intake, or drinking despite negative consequences. Previous studies have shown that female rodents have a heightened vulnerability to drug use across different stages of the addictive cycle, but no previous studies have studied females in a model of aversion-resistant alcohol intake. Here, we investigated sex differences in binge-like and aversion-resistant alcohol drinking in C57BL/6J mice using a modified drinking-in-the-dark (DID) paradigm.

In Experiment 1, 24-hour aversion to quinine (0, 100, or 250 μM) was assessed. In Experiment 2, male and female adult C57BL/6J mice consumed 15% ethanol (EtOH) or water in a 2-bottle limited-access DID paradigm for 2 h/d for 15 days. The EtOH was next adulterated with quinine (0, 100, or 250 μM) over 3 consecutive drinking sessions to test aversion-resistant intake. In Experiment 3, intake of quinine-adulterated (100 μM) EtOH was assessed across all 15 drinking sessions.

Quinine was equally aversive to both sexes in Experiment 1. In Experiment 2, female mice consumed significantly more alcohol than male mice during the final 6 drinking sessions. Levels of aversion-resistant intake did not differ between the sexes. In Experiment 3, quinine suppressed consumption in all mice, though females drank significantly more on the final 2 sessions.

The results of this study demonstrate that while female mice escalate and consume more EtOH than males, both sexes exhibit similar levels of aversion-resistant drinking. These results inform our understanding of how sex interacts with vulnerability for addiction and argue for the inclusion of females in more studies of aversion-resistant alcohol drinking.