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

Alcohol Clin Exp Res. 2019 Feb;43(2):243-249. doi: 10.1111/acer.13923. Epub 2018 Dec 9.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Compulsive; Drinking in the Dark; Ethanol; Mouse; Quinine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / prevention & control*
  • Alcohol Drinking / psychology
  • Animals
  • Avoidance Learning / drug effects*
  • Binge Drinking / prevention & control*
  • Binge Drinking / psychology
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Mice
  • Quinine / pharmacology*
  • Sex Characteristics


  • Quinine