The persistent effects of exposure to a predator odor stressor on sensitivity to alcohol.

Traumatic stress is linked to problematic alcohol use, yet its persistent effects on alcohol sensitivity remain unclear. This study examined the long-term effects of traumatic stress on alcohol sensitivity in male and female Long-Evans rats. Rats were trained to discriminate alcohol (2 g/kg, i.g.) from water, and two weeks after a single, inescapable exposure to the predator odor stressor TMT, substitution for an alcohol dose curve and GABA agonism were assessed both systemically (pentobarbital, i.p.) and site-specifically [muscimol in the prelimbic cortex (PrL) or anterior insular cortex (aIC)]. Additional experiments in alcohol-naive rats examined the effects of TMT on alcohol-induced behaviors, c-Fos expression, and GABA receptor gene expression in the PrL and aIC. TMT exposure produced a leftward shift in the alcohol dose-response curve, indicating increased interoceptive sensitivity to alcohol in males, but not females. The alcohol-like effects of systemic pentobarbital were unaltered by TMT exposure. TMT reduced expression and increased c-Fos in the PrL of males, whereas TMT increased expression without altering c-Fos in the PrL of females. Alcohol-induced effects on locomotion and startle response were not observed in the TMT-exposed group when analyzed in both sexes. These findings highlight sex-specific effects of traumatic stress on alcohol sensitivity, with evidence that stress-induced PrL GABA adaptations may contribute to increased interoceptive sensitivity to alcohol in males. These results may help to better understand the association between traumatic stress and alcohol use disorder (AUD).