Individual differences in behavioral responses to predator odor predict subsequent stress reactivity in female rats

Stress-induced neuropsychiatric disorders are among the most prevalent medical conditions and have widespread effects on both patients and society. Females experience over twice the rates of stress-related anxiety and depression when compared to males and often exhibit worse symptomatology and treatment outcomes. However, preclinical experiments exploring the neurobiological mechanisms of stress susceptibility in females have been traditionally understudied. Previous data from our lab has determined that females are selectively vulnerable to the consequences of vicarious witness stress, and these experiments were designed to determine specific behavioral and physiological factors that could predict which groups would be more susceptible to the effects of stress. Adult, female, Sprague-Dawley rats were first exposed to a ferret predator odor to determine baseline individual differences in behavioral responses. Rats were stratified by the duration of freezing behavior exhibited in response to the ferret odor and equally balanced into non-stressed controls and vicarious witness stress exposed groups. These female rats were then assessed on a battery of behavioral tasks including sucrose preference, elevated plus maze, acoustic startle, and the ferret odor and witness stress cue exposures to determine if baseline differences in stress responding can predict the behavioral response to future stress and stress cues. High freezing in response to the ferret odor was associated with behavioral sensitization to witness stress and hypervigilant responses to stress cues that was accompanied by exaggerated neuroimmune responses. These experiments establish a powerful behavioral predictor of stress susceptibility in females and begin to address neurobiological correlates that underlie this response.