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


OBJECTIVE
The aim of this study was to investigate the effects of exogenous NO in CMS-induced depression in young adult mice.


RESULTS
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.


CONCLUSIONS
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.
Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 210029, China.
Yao
Y
Hua
Xin-Yan
XY
Huang
Li
L
Zhou
Qi-Gang
QG
Zhou
Yao
Y
Hu
Chun-Xia
CX
Luo
Fei
F
Li
Dong-Ya
DY
Zhu
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D009603:Nitroso Compounds / Q000494:pharmacology*; D013315:Stress, Psychological; D015215:Zidovudine / Q000494:pharmacology
D000928:Antidepressive Agents; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D015215:Zidovudine; D052248:Nitric Oxide Synthase Type I