DETA/NONOate, a nitric oxide donor, produces antidepressant effects by promoting hippocampal neurogenesis

Abstract

Increasing evidence suggests that depression may be associated with a lack of hippocampal neurogenesis. Our recent study shows that endogenous nitric oxide (NO) contributes to chronic mild stress (CMS)-induced depression by suppressing hippocampal neurogenesis. The aim of this study was to investigate the effects of exogenous NO in CMS-induced depression in young adult mice. In normal mice, administration of a pure NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA/NONOate; 0.4 mg/kg, i.p., for 7 days) produced an antidepressant-like effect and significantly increased hippocampal neurogenesis. The mice exposed to CMS exhibited behavioral changes typical of depression and impaired neurogenesis in the hippocampus. Treatment with DETA/NONOate (0.4 mg/kg, i.p., for 7 days) reversed CMS-induced behavioral despair and hippocampal neurogenesis impairment. We treated mice with a telomerase inhibitor 3′-azido-deoxythymidine (AZT; 100 mg/kg, i.p., for 14 days) to disrupt neurogenesis. From day 4 to day 11 of AZT treatment, mice were injected with DETA/NONOate (0.4 mg/kg, i.p., for 7 days). Disrupting hippocampal neurogenesis blocked the antidepressant effect of DETA/NONOate. Our findings suggest that exogenous NO benefits chronic stress-induced depression by stimulating hippocampal neurogenesis and may represent a novel approach for the treatment of depressive disorders.

DOI: 10.1007/s00213-008-1200-1

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@article{Hua2008DETANONOateAN, title={DETA/NONOate, a nitric oxide donor, produces antidepressant effects by promoting hippocampal neurogenesis}, author={Yao Hua and Xin-Yan Huang and Li Zhou and Qi-Gang Zhou and Yao Hu and Chun-Xia Luo and Fei Li and Dong-Ya Zhu}, journal={Psychopharmacology}, year={2008}, volume={200}, pages={231-242} }