Childhood trauma and post-trauma environment affect fear memory and alcohol use differently in male and female mice.

Background: Childhood trauma is associated with the development of adult mental health and substance use disorders, with females generally being more at risk. Alcohol is commonly used for coping with trauma, and alcohol use disorder (AUD) affects ∼14.4 million adult Americans annually. Research investigating sex differences in the environmental modification of anxiety and alcohol use following childhood trauma will extend our understanding of the etiology of AUD. Here, we sought to model the interacting effects of a single-episode late childhood trauma with post-trauma environment on adult alcohol use using male and female mice.

Methods: C57Bl6/J mice (d22) exposed to predator odor (TMT) or water were reared in standard environments (SE) or environmental enrichment (EE). Mice were assessed for adolescent anxiety and conditioned fear, and for adult alcohol use in a limited access, response non-contingent, alcohol exposure paradigm.

Results: A single exposure to predator odor was an effective stressor, inducing long-term sex-dependent changes in conditioned fear and alcohol behaviors that interacted with post-trauma environment. Adolescent EE females showed more conditioned freezing to the trauma-associated context. Adult EE mice consumed less total alcohol than SE mice. However, alcohol use across time differed for males and females. Exposure to a childhood stressor increased alcohol use significantly in females, but not males. EE males, but not EE females, drank less than SE counterparts.

Conclusions: Findings from this model recapitulate greater vulnerability to childhood trauma in females and support sex differences in post-trauma development of conditioned fear and alcohol use that are modified by environment.