Original articleTelmisartan attenuates diabetes induced depression in rats

BackgroundRole 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.MethodsDiabetes was induced by injecting streptozotocin. After 21 days 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 (0.05 mg/kg, po) or metformin (200 mg/kg, po) or fluoxetine (20 mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21 days 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).ResultsPersistent 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).ConclusionsLow 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.

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