Single prolonged stress in mice: interactions between alcohol drinking, negative affect, and fear learning

SPS selectively increased negative affect and startle responses in male mice, while females were unaffected. SPS disrupted discrimination adjustment between fear and safety cues during extinction, while ethanol exposure attenuated overall fear responses. SPS maintained baseline sex differences in consumption. Furthermore, female consumption increased when access was provided prior to and continuously throughout SPS and fear conditioning, contrasting with groups exposed to ethanol afterwards. In summary, we identified a distinct sex specific relationship between traumatic stress, fear memory, and the timing of ethanol consumption. We highlight SPS as a robust translational model for exploring the sex-specific neurobiological mechanisms driving traumatic stress-induced affective disturbances.