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

In rats subjected to the forced swimming test, ketamine at 10 mg/kg reduced immobility time, an indicator of antidepressant-like effect, and lowered hippocampal nitric oxide (NO) levels. The NO precursor L-arginine increased NO and blocked ketamine's behavioral effect, while the NO synthase inhibitor L-NAME enhanced the effect of a low ketamine dose (3 mg/kg) and also reduced NO. These findings suggest that ketamine's antidepressant action involves suppression of the L-arginine/nitric oxide pathway.

Study at a glance

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