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Candesartan reverses depression‐like behavior in a rodent model of depression
Author(s) -
Stedenfeld Kristen A,
Clinton Sarah M,
Kerman Ilan A,
Akil Huda,
Watson Stanley J,
Sved Alan F
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1052.3
Subject(s) - candesartan , depression (economics) , antidepressant , medicine , endocrinology , behavioural despair test , antagonist , cardiology , psychology , angiotensin ii , receptor , hippocampus , economics , macroeconomics
Depression and cardiovascular disease (CVD) share a bidirectional relationship wherein the presence of one increases the likelihood of the other. Antagonists of the renin‐angiotensin system (RAS) that are useful in treating CVD may also have antidepressant properties. Therefore, the current study examined the impact of chronic treatment with an AT1 receptor antagonist on behavioral and cardiovascular parameters in a rodent model of depression. Rats selectively bred for low locomotion in a novel environment have been shown previously to be particularly vulnerable to develop depression‐like behavior in response to chronic mild intermittent variable stress (CMS). Rats were exposed to 4 weeks of CMS and anhedonic behavior was assessed via weekly sucrose preference tests (SPT). Heart rate (HR) and HR variability (HRV), a clinically relevant measure of autonomic function, were measured by radiotelemetry. Previously demonstrated effects of CMS (reduced SPT scores, increased HR, decreased HRV) were observed. Candesartan (0.5mg/kg/day, sc infusion) or vehicle was administered and CMS was continued. In CMS‐exposed rats, candesartan markedly improved SPT scores and reduced measures of anxious behavior. These results suggest that the RAS might be a useful therapeutic target for the treatment of co‐morbid depression and CVD. [N000140210879, NIDA 5P01DA021633 (HA) 1K99MH081927, NARSAD Young Investigator (IAK)]