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 DOI: 10.3760/cma.j.issn.1674-6554.2012.09.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 42 |
| Population | Male Wistar rats |
| Interventions | Ketamine L-Arginine L-NAME |
| Dose | 3 mg/kg, 10 mg/kg, 750 mg/kg, 30 mg/kg |
| Topics | Ketamine Esketamine |
| Keywords | Behavioural despair test Saline Nitric oxide synthase Arginine Endocrinology Antidepressant Anesthesia Biochemistry Hippocampus Amino acid |
| Key findings | Ketamine's antidepressant effects are related to 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
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |