Depressive and cardiovascular disease comorbidity in a rat model of social stress: a putative role for corticotropin-releasing factor.
BACKGROUND
Depression is associated with medical comorbidities, particularly cardiovascular disease. However, mechanisms linking depression and cardiovascular disease remain unclear.


OBJECTIVE
This study investigated whether the rat resident-intruder model of social stress would elicit behavioral dysfunctions and autonomic changes characteristic of psychiatric/cardiovascular comorbidity. Furthermore, the efficacy of the corticotropin-releasing factor-1 (CRF(1)) receptor antagonist, NBI-30775 (NBI), or the tricyclic antidepressant, desipramine (DMI), to prevent social stress-induced behavioral, neuroendocrine, and cardiovascular changes were evaluated.


METHODS
Adult male rats were exposed to resident-intruder stress (seven consecutive days) and systemically administered NBI (10 mg/kg/7 days), DMI (10 mg/kg/14 days), or vehicle. The efficacy of NBI and DMI to alter the behavioral and neuroendocrine responses to social stress was assessed. Furthermore, their effects on stress-induced forced swim behavior (FST), bladder and adrenal weight, and heart rate variability (HRV) were examined.


RESULTS
NBI, but not DMI, increased time spent in an upright, defensive posture and the latency to submit to the resident. Additionally, only NBI reduced social stress-induced adrenocorticotropic hormone and corticosterone release. Social stress increased FST immobility, caused bladder and adrenal hypertrophy, and decreased HRV. Both NBI and DMI blocked stress-induced increases in immobility during the FST. However, only NBI inhibited social stress-induced adrenal and bladder hypertrophy and decreases in heart rate variability.


CONCLUSIONS
Rat resident-intruder stress paradigm models aspects of psychiatric/medical comorbidity. Furthermore, the CRF system may contribute to both the behavioral response during social stress and its behavioral and autonomic consequences, offering insight into potential therapy to treat these comorbid conditions.
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. susankwood2@gmail.com
Susan K
SK
Wood
Kile V
KV
McFadden
Dimitri
D
Grigoriadis
Seema
S
Bhatnagar
Rita J
RJ
Valentino
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000150:complications / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003863:Depression / Q000150:complications / Q000503:physiopathology*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D012919:Social Behavior; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*; D000099052:CRF Receptor, Type 1
D000929:Antidepressive Agents, Tricyclic; D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D003891:Desipramine