Elizabeth A Sneddon1, Robert D White1, Anna K Radke1,2. 1. Department of Psychology , Miami University, Oxford, Ohio. 2. Center for Neuroscience and Behavior , Miami University, Oxford, Ohio.
Abstract
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.
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.
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