Effects of predator odor stress on alcohol-induced conditioned taste aversion and lateral habenula cFos expression in rats.

Stress-related disorders and alcohol use disorder (AUD) frequently co-occur, yet the mechanisms linking stress coping styles to alcohol sensitivity remain unclear. Here, we tested whether acute stress exposure alters sensitivity to alcohol's aversive effects, an important factor in regulating drinking, and alcohol-induced neural activation in the lateral habenula (LHb), a brain region implicated in negative valence processing. Male and female rats were exposed to acute predator odor stress and classified as Avoiders or Non-Avoiders based on post-stress avoidance behavior. Alcohol-induced conditioned taste aversion (CTA) and alcohol challenge-evoked cFos expression in the LHb, lateral hypothalamus (LH), and central amygdala (CeA) were quantified. Female Non-Avoiders developed alcohol-induced CTA after a single conditioning session, whereas Avoiders and unstressed Controls did not, suggesting heightened sensitivity to alcohol's aversive properties in this group. No stress-related differences in CTA were observed in males. Alcohol challenge decreased LHb cFos expression in female rats across groups and selectively in male Avoiders, suggesting sex- and avoidance-dependent modulation of LHb activity. Although there were no alcohol or stress group effects on cFos in the LH or CeA, there were significant correlations in cFos expression between LH-LHb and CeA-LH. These findings suggest that stress-induced individual differences in avoidance behavior predict alcohol sensitivity and LHb responsivity in a sex-dependent manner, with implications for understanding how stress-related coping phenotypes influence vulnerability to alcohol misuse.