Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor.
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.
The Children's Hospital of Philadelphia, Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Susan K
SK
Wood
Hayley E
HE
Walker
Rita J
RJ
Valentino
Seema
S
Bhatnagar
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D016000:Cluster Analysis; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D004291:Dominance-Subordination; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D017403:In Situ Hybridization; D007206:Individuality; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone