Early life stress paired with adolescent alcohol consumption reduces two-bottle choice alcohol consumption in mice

In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). We previously used an infant footshock model in rats that produces stress-enhanced fear learning (SEFL) and increases aversion-resistant alcohol drinking to explore this shared predisposition. The goal of the current study was to test the viability of this procedure as a model of comorbid PTSD and AUD in male and female C57BL/6J mice.

Acute ELS was induced using 15 footshocks on postnatal day (PND) 17. In adulthood, alcohol drinking behavior was tested in one of three two-bottle choice drinking paradigms. In continuous access, mice were given 24 h access to 5% and 10% ethanol and water for five consecutive drinking sessions each. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions 3 h into the dark cycle. 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, 100, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Intermittent access drinking was tested with and without a period of adolescent drinking (PND 35).

Infant footshock did not alter drinking in the continuous or limited access tasks. In the intermittent access task, adult consumption and preference were lower in shocked mice when adolescent drinking was included. Aversion resistance was greater in females following infant footshock and adolescent drinking.

Our results demonstrate that ELS, in the form of infant footshock on PND 17, must be followed by a period of adolescent drinking to affect adult alcohol consumption in mice.