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_A 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_A 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 Gabra1 expression and increased c-Fos in the PrL of males, whereas TMT increased Gabra1 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_A 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).