A comparison of activation patterns of cells in selected prefrontal cortical and amygdala areas of rats which are more or less anxious in response to predator exposure or submersion stress.

This study had two purposes. First: to compare predator and water submersion stress cFos activation in medial prefrontal cortices (mPFC) and the medial amygdala (MeA). Second: to identify markers of vulnerability to stressors within these areas. Rats were either predator or submersion stressed and tested 1.75 h later for anxiety. Immediately thereafter, rats were sacrificed and cFos expression was examined. Predator and submersion stress equally increased anxiety-like behavior in the elevated plus maze (EPM) and hole board. To examine vulnerability, rats which were less anxious (LA) and more (highly) anxious (MA) in the EPM were selected from among handled control and stressed animals. LA stressed rats were considered stress non-responsive while MA stressed rats were considered stress responsive. Predator stress, but not submersion stress, activated MeA cFos. CFos expression of mPFC cells was elevated in LA rats and reduced in MA rats in predator stressed animals only, correlating negatively with anxiety. These findings are consistent with data implicating greater mPFC excitability in protection against the effects on affect of traumatic stress. The findings also suggest that this conclusion is stressor specific, applying to predator stress but not submersion stress. Both stressors have been suggested to model hyperarousal and comorbid anxiety aspects of PTSD in humans. Hence the use of these paradigms to identify brain bases of vulnerability and resilience to traumatic stress in PTSD has translation potential. On the other hand, our evidence of stressor specificity of vulnerability/resilience markers raises a caution. The data suggest that preclinical markers of vulnerability/resilience in a given stress paradigm are at best suggestive, and translational value must ultimately be confirmed in humans.