Considerable progress has been made in understanding neural circuits and processes responsible for chronic stress habituation, sensitization and pathology. However, the neural trigger that differentiates successful from unsuccessful coping remains elusive. Uncovering processes underlying the transition from adaptation and pathology bears consideration of what constitutes “adaptation” and “pathology,” as many responses and behaviors that may appear “maladaptive” make perfect sense in the appropriate context. Indeed, context-inappropriate physiological and emotional responses are hallmarks of stress-related disorders (depression, PTSD). Moving forward, animal models will need to incorporate an appreciation of the relevance of physiologic and behavioral endpoints to the normal repertoire of the organism under conditions of challenge, and develop testing conditions that can more clearly query how chronic stress can generate situationally inappropriate responses reminiscent of human pathology.
