Depression-like Effect of Telmisartan in Mice Forced Swim Test: Involvement of Brain Monoaminergic System

摘要

The effect of acute treatment of telmisartan, an angiotensin AT_1 receptor blocker at various doses (0.01, 0.05, 0.1, 1, 5, 10 and 20 mg kg~(-1), p.o.) on immobility in mice forced swim test has been studied. In addition, telmisartan in combination with fluoxetine hydrochloride, reserpine, haloperidol and reboxetine has also been studied on immobility. In the present study, telmisartan per se elicits significant bell shaped dose dependent depression- like effect in the forced swim test. In the drug-interaction studies, telmisartan (0.1, 1 and 5 mg kg~(-1), p.o.) significantly reversed the fluoxetine hydrochloride and reboxetine-induced immobility. Telmisartan, at same doses potentiated the reserpine and haloperidol-induced immobility in the forced swim test. The depression-like effect produced by telmisartan in the forced swim test in mice might be due to the unopposed AT_2 receptor stimulation because of the complete blockade of AT_1 receptor even at the low doses of telmisartan. The obtained results in the drug-interaction studies revealed the neuromodulatory effect of telmisartan on brain monoaminergic system.