Valsartan reverses depressive/anxiety-like behavior and induces hippocampal neurogenesis and expression of BDNF protein in unpredictable chronic mild stress mice

Valsartan is a synthetic non-peptide angiotensin II type 1 receptor antagonist that dilates blood vessels and reduces blood pressure by blocking the action of angiotensin, and is safe and well tolerated in hypertensive patients. Population-based studies have suggested a positive role of sartans in reducing the risk of depression. This study aimed at investigating the effects of valsartan on unpredictable chronic mild stress (UCMS) mice by means of open-field test (OFT), novel-suppressed feeding test (NSF), tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). The effects of valsartan on antidepression/antianxiety, hippocampal neurogenesis and BDNF expression were evaluated in these behavior tests. Chronic administration of valsartan (5-40 mg/kg/d, p.o.) increased the time spent in the center of the field in OFT and the latency to eat in NSF, reduced the immobility time in both TST and FST, and increased the sucrose preference in SPT. A similar effect was observed in the positive control group of which the mice were treated with imipramine (30 mg/kg/d, i.p.) and tested by OFT, NSF, TST, FST and SPT. In this study, an impairment in hippocampal neurogenesis which parallelled with a reduced BDNF level in the hippocampus was observed in the mice that were treated with UCMS for 6 weeks. But the proliferation of progenitor cells and generation of new hippocampal neurons were restored after these mice were treated with valsartan (40 mg/kg/d, p.o.) for 4 weeks. These findings demonstrate that valsartan is an effective antidepressant/antianxiety reagent and can promote the hippocampal neurogenesis and expression of BDNF.