, 200:231 | Cite as

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

  • Yao Hua
  • Xin-Yan Huang
  • Li Zhou
  • Qi-Gang Zhou
  • Yao Hu
  • Chun-Xia Luo
  • Fei Li
  • Dong-Ya ZhuEmail author
Original Investigation



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.


Depression Nitric oxide Stress Neurogenesis Hippocampus Antidepressant Mice Behavior Dentate gyrus BrdU 



This work was supported by grants (to Dong-Ya Zhu) from the National Natural Science Foundation of China (30371640 and 30572174) and from the Natural Science Foundation of Jiangsu Province (BK 2007728).

Conflict of interest

The authors declare that no conflict of interest exists.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Yao Hua
    • 1
  • Xin-Yan Huang
    • 1
  • Li Zhou
    • 1
  • Qi-Gang Zhou
    • 1
  • Yao Hu
    • 1
  • Chun-Xia Luo
    • 1
  • Fei Li
    • 1
  • Dong-Ya Zhu
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacology, School of PharmacyNanjing Medical UniversityNanjingChina
  2. 2.Key Lab of Human Functional Genomics of Jiangsu ProvinceNanjing Medical UniversityNanjingChina

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