Anti-depressant effects of losartan on chronic unpredicted mild stress induced depression rat model

Abstract

Objective To investigate effect of losartan (Los) on the behavior change of chronic unpredicted mild stress (CUMS) model rats, anti-inflammatory and antioxidant action, and explore its potential antidepressant mechanism. Methods Sprague-Dawley rats were randomly divided into 4 groups: Control group, Los group, CUMS group, and CUMS+Los group. The rats in Los group and CUMS+Los group were continuously administrated with losartan (10 mg/kg) by gavage and those in Control group and CUMS group received an equal volume of saline for 8 weeks. Sucrose preference test (SPT), forced swim test (FST) and elevated plus maze (EPM) were performed to evaluate depression-like behaviors in rats. Enzyme-linked immunosorbent assay was used to examine angiotensin Ⅱ (Ang Ⅱ) levels. RT-PCR was used to detect the mRNA expression level of Ang Ⅱ type 1 receptor (AT1R), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). The activity of superoxide dismutase (SOD) and content of malonyldialdehyde (MDA) by spectrophotometry. Results There was no significant difference in consumption amount of sugar water, time spent in the open arms, number and ratio of open arm entries, immobility time in FST, the level of Ang Ⅱ and expression of AT1R, IL-6, TNF-α, activity of SOD and the content of MDA between LOS group and Control group (P>0.05). Compared to the Control group, CUMS showed significantly decreased in consumption amount of sugar water, time spent in the open arms, number and ratio of open arm entries, activity of SOD and significantly increased immobility time in FST, the level of Ang Ⅱ and expression of AT1R, IL-6, TNF-α, the content of MDA, and the difference was statistically significant (P<0.05). The consumption amount of sugar water, time spent in the open arms, number and ratio of open arm entries, activity of SOD in CUMS+Los group were higher than that in Control group, the immobility time in FST, the level of Ang Ⅱ and expression of AT1R, IL-6, TNF-α, the content of MDA in CUMS+Los group were lower than that in Control group, and the difference was statistically significant (P<0.05). Conclusion Losartan can improve the depression-like behaviors of CUMS rat obviously, diminish inflammation and prevent oxygenated stress damage, which may be related to the Renin-angiotensin-system in brain and provide a new direction for the treatment of depression. Key words: Losartan; Chronic unpredictable mild stress; Depression