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Role of L-arginine/nitric oxide pathway in the antidepressant effects of ketamine

Guang-Fen Zhang, Nan Wang, Jinyun Shi, Xiaomin Li, Xu Shixia, Zhiqiang Zhou

Zhonghua xingwei yixue yu naokexue zazhi September 20, 2012 Peer reviewed DOI: 10.3760/cma.j.issn.1674-6554.2012.09.008 via OpenAlex

Summary

The study investigated how the L-arginine/nitric oxide pathway affects the antidepressant effects of ketamine in rats. It found that ketamine significantly reduced immobility time in a forced swimming test, indicating antidepressant effects, with the 10 mg/kg dose (91.3 seconds) showing notable improvement compared to the control group (139.0 seconds). Additionally, levels of nitric oxide were altered in treated groups, suggesting a link between ketamine's effects and the suppression of this pathway.

Study at a glance

Design randomized controlled trial
Sample size 42
Population male Wistar rats
Key finding The antidepressant effects of ketamine are related to the suppression of the L-arginine/nitric oxide pathway.

Abstract

Objective To study the role of L-arginine/nitric oxide (NO) pathway in the antidepressant effects of ketamine. Methods Forty two male Wistar rats (200-250 g) were equally randomized into 7 groups (n=6): control group (C group), L-Arginine (a precursor of NO) group (LA group), L-NAME(an non-selectivity inhibitor of NO synthase) group (LN group), ketamine 3 mg/kg group (K3 group), ketamine 10 mg/kg group (K10 group), L-Arginine + ketamine 10 mg/kg group(LAK10 group), L-NAME + ketamine 3 mg/kg group(LNK3 group). The forced swimming test (FST) of 15 min (pre-test session) was used to establish a rat depression model, then twenty-four hours later FST (test session) was carried out of 6 min and the immobility time in last 5 min was recorded. All the groups were pretreated with saline 1.0 ml, L-arginine 750 mg/kg or L-NAME 30 mg/kg 90 min before FST. Saline 1.0 ml, ketamine 3.0 mg/kg or ketamine 10.0 mg/kg were injected 60 min before FST. The content of hippocampal NO was detected immediately after ethology measurement. Results Compared with C group (immobility time: (139.0±27.6)s), the immobility time decreased significantly ((85.5±34.2), (91.3±31.6)s) in K10 group and LNK3 group (P 0.05); compared with C group ((0.61±0.21) μmol/gProt), the content of NO increased in LA group ((1.09±0.39) μmol/gProt) and decreased in K10 group and LNK3 group significantly((0.28±0.12), (0.31±0.14) μmol/gProt)(P 0.05). Conclusion The antidepressant effects of ketamine are related to the suppression of L-arginine/nitric oxide pathway. Key words: Ketamine; Depression; L-arginine; Nitric oxide

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