Sex, but not early life stress, effects on two-bottle choice alcohol drinking behaviors in mice

In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). We have previously used an infant footshock model to explore this shared predisposition. Infant footshock produces stress-enhanced fear learning (SEFL) in rats and mice and increases aversion-resistant alcohol drinking in rats. The goal of the current study was to extend this model of comorbid PTSD and AUD to male and female C57BL/6J mice. Acute ELS was induced using 15 foot-shocks on postnatal day 17. In adulthood, after PND 90, ethanol drinking behavior was tested in one of three two-bottle choice drinking paradigms: continuous access, limited access drinking in the dark, or intermittent access. In continuous access, mice were given 24 h access to 5% or 10% ethanol and water. Each ethanol concentration was provided for five consecutive drinking sessions. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions. Ethanol was provided 3 h into the dark cycle to maximize task engagement when mice are most active. In intermittent access, mice were presented with 20% ethanol and water Monday, Wednesday, and Friday, for four consecutive weeks. In a fifth week of intermittent access drinking, increasing concentrations of quinine (10 mg/L, 100 mg/L, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Our results indicate that infant footshock does not influence adult ethanol consumption in mice. Infant footshock did not affect ethanol-only consumption or preference in any of the three drinking paradigms. Further, and in contrast to our previous results in rats, infant footshock did not appear to influence consumption of quinine-adulterated ethanol. The biological sex of the mice did affect ethanol-only consumption in all three drinking paradigms, with females consuming more ethanol than males. Preference for ethanol vs. water was higher in females only under continuous access conditions. Our results suggest that infant footshock alone may not be sufficient to increase drinking levels in mice. We hypothesize that infant footshock may require a secondary, adolescent stress exposure to influence ethanol drinking behavior. Further research is needed to create a valid model of PTSD-AUD comorbidity in male and female mice.