Lasting anxiogenic effects of feline predator stress in mice: Sex differences in vulnerability to stress and predicting severity of anxiogenic response from the stress experience

Previous work in male Swiss Webster (CFW) mice demonstrated a long lasting effect of predator stress on risk assessment in the elevated plus maze (EPM). Most severe effects (increases in risk assessment) were seen following a brief unprotected exposure to a cat. Lesser effects were produced by a brief exposure of mice to the cat exposure room without a cat in the room (room stress). This graded response is analogous to the covariation of symptom severity and severity of the precipitating stressor in posttraumatic stress disorder (PTSD). The present study extended these findings to another strain of mice, C57/BL6, and a broader range of tests of anxiety-like behavior, including EPM, acoustic startle response and light/dark box test. Sex was introduced as a variable to investigate if females might be more susceptible to the effects of stressors than males, as has been suggested in human PTSD. Graded and lasting (7 days) effects of a 10 min exposure to a cat (predator stress) or to the cat exposure room only (room stress) were observed on lighted chamber avoidance in the light/dark box. Room stress was without effect on startle responses, but predator stress enhanced peak startle amplitudes measured in the light or in the dark. There was no evidence of light-enhancement of startle in C57 mice. Female mice were more susceptible to the effects of predator and room stress, depending on the measure. Females only responded to cat exposure with a lasting increase in average startle amplitude. This was due to an increased and more prolonged multipeak response to startle after the first and maximal peak startle response. In addition, in females, room and predator stress were equally anxiogenic in measures of open arm avoidance in the EPM. In contrast, room stress was without effect on open arm avoidance in males, but cat exposure was as anxiogenic in males as it was in females. These findings suggest EPM anxiety in females is affected more by the milder stress of room exposure. Severity of effects of predator stress on anxiety-like behaviors in EPM and startle were well predicted (60% of the variance) by measures of cat behavior and probability of mouse defensive response to particular cat behaviors during the cat exposure. Finally, factor analysis indicated that different tests of anxiety-like behavior may be measuring different and independent aspects of mouse affect. Moreover, stressors had no lasting effects on sugar solution consumption. Implications of these findings for modeling PTSD and using transgenic strains of mice to study lasting effects of stress on affect are discussed.