Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor

Endocrinology. 2010 Apr;151(4):1795-805. doi: 10.1210/en.2009-1026. Epub 2010 Feb 16.


Previous social stress exposure is a common risk factor for affective disorders. However, factors that determine vulnerability or resiliency to social stress-induced psychopathologies remain unclear. Using a rodent model of social stress, the present study was designed to identify putative neurobiological substrates that contribute to social stress-induced psychopathology and factors that influence or predict vulnerability. The resident-intruder model of defeat was used as a social stressor in adult male Sprague Dawley rats. The average latency to assume a subordinate posture (signaling defeat) over seven daily defeat exposures was calculated and examined with respect to endpoints of hypothalamic-pituitary-adrenal activity, components of the corticotropin-releasing factor (CRF) system, and behaviors that are relevant to human depression. In the present studies, a bimodal distribution emerged in an otherwise homogeneous population of Sprague Dawley rats such that 42% of rats exhibited short defeat latencies (<300 sec), whereas 58% of rats resisted defeat and exhibited longer latencies (>300 sec). These two phenotypes were associated with distinct endocrine and behavioral profiles as well as differences in components of the CRF system. Notably, the short-latency subpopulation exhibited hypothalamic-pituitary-adrenal dysregulation and behavior similar to that observed in melancholic depression. Examination of components of the CRF system suggested that proactive behavior in resisting defeat exhibited by long-latency rats was associated with decreased efficacy of CRF. Together, these data suggest that inherent differences in stress reactivity, perhaps as a result of differences in CRF regulation, may predict long-term consequences of social stress and vulnerability to depressive-like symptoms.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Analysis of Variance
  • Animals
  • Arginine Vasopressin / genetics
  • Arginine Vasopressin / metabolism
  • Behavior, Animal / physiology
  • Body Weight / physiology
  • Cluster Analysis
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism*
  • Depression / metabolism*
  • Dominance-Subordination*
  • Hypothalamo-Hypophyseal System / metabolism
  • In Situ Hybridization
  • Individuality*
  • Male
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Pituitary Gland / metabolism
  • Pituitary-Adrenal System / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Restraint, Physical / physiology
  • Stress, Physiological / physiology
  • Stress, Psychological / metabolism*
  • Time Factors


  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Arginine Vasopressin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone