title: Telmisartan attenuates diabetes induced depression in rats.
abstract: BACKGROUND
  Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats.
  
  
  METHODS
  Diabetes was induced by injecting streptozotocin. After 21days of treatment the rats were subjected to forced swim test (FST). The rats, with increased immobility time, were considered depressed and were treated with vehicle or TMS (0.05mg/kg, po) or metformin (200mg/kg, po) or fluoxetine (20mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21days of treatments, FST, open field test (OFT) and elevated plus maze (EPM) paradigm were performed. Blood was drawn to estimate serum cortisol, nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-1β).
  
  
  RESULTS
  Persistent hyperglycemia resulted in depression and anxiety in rats as observed by increased immobility, reduced latency for immobility, reduced open arm entries and time spent. The depressed rats showed a significant rise in serum cortisol, NO, IL-6 and IL-1β (p<0.001). TMS antagonized depression and anxiety. It also significantly attenuated serum cortisol, NO, IL-6 and IL-1β (p<0.001).
  
  
  CONCLUSIONS
  Low dose TMS and its combination with metformin normalizes depressive mood, reduces pro-inflammatory mediators and ameliorates the HPA axis function; thereby providing beneficial effects in DID.
authors.affiliation: Department of Pharmacology, Sinhgad Institute of Pharmacy, Narhe, Pune, India. Electronic address: aswarurmila@gmail.com.
authors.forename: Urmila
authors.initials: U
authors.lastname: Aswar
authors.affiliation: Department of Pharmacology, Sinhgad Institute of Pharmacy, Narhe, Pune, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Chepurwar
authors.affiliation: Department of Pharmacology, Sinhgad Institute of Pharmacy, Narhe, Pune, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Shintre
authors.affiliation: Department of Pharmacology, Sinhgad Institute of Pharmacy, Narhe, Pune, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Aswar
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D013311:Streptozocin / Q000494:pharmacology; D013550:Swimming; D000077333:Telmisartan
chemical_list: D000928:Antidepressive Agents; D001562:Benzimidazoles; D001565:Benzoates; D053583:Interleukin-1beta; D015850:Interleukin-6; D005473:Fluoxetine; D009569:Nitric Oxide; D013311:Streptozocin; D008687:Metformin; D000077333:Telmisartan; D006854:Hydrocortisone
keywords: Brain renin angiotensin system; Diabetes induced depression; HPA axis; Telmisartan