Role of the nitric oxide donor sodium nitroprusside in the antidepressant effect of ketamine in mice.
Miriam A Vogt, Anne S Vogel, Natascha Pfeiffer, Peter Gass, Dragoš Inta
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology October 1, 2015 DOI: 10.1016/j.euroneuro.2015.06.012 via PubMed
Summary
AI-generated from the abstractKetamine is a fast-acting antidepressant but can cause psychosis-like side effects. The nitric oxide donor sodium nitroprusside (SNP) prevents such effects in rats and humans. In mice, pre-treatment with SNP (0.5-1 mg/kg) did not alter the antidepressant effect of ketamine (30 mg/kg) in the Porsolt Forced Swim Test, and SNP alone had no effect. This suggests the nitrinergic system may be differentially involved in ketamine's antidepressant versus psychotomimetic effects, though species differences cannot be ruled out.
Study at a glance
| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Sodium nitroprusside Ketamine |
| Dose | SNP 0.5-1 mg/kg i.p.; ketamine 30 mg/kg |
| Topics | Depression Ketamine |
| Keywords | Nmda receptor Nitric oxide Psychosis |
| Key finding | Pre-treatment with SNP did not alter the antidepressant effect of ketamine in mice, suggesting differential involvement of the nitrinergic system in ketamine's antidepressant versus psychotomimetic effects. |
Abstract
Ketamine may represent an efficient alternative antidepressant with rapid therapeutic onset; however, the clinical use of ketamine is hampered by psychosis-like side-effects. Recent studies suggest that the nitric oxide (NO) donor sodium nitroprusside (SNP) prevents psychosis-like abnormalities triggered by ketamine or another NMDA receptor (NMDAR) antagonist, phencyclidine (PCP) in rats. SNP was shown to elicit antipsychotic effects also in humans. Considering the tight interrelation between NMDAR activation and neuronal NO synthesis, we evaluated the effect of pre-treatment with SNP on the antidepressant action of ketamine. We found that SNP (0.5-1mg/kg, i.p.) did not alter the antidepressant effect of ketamine (30 mg/kg) in the Porsolt Forced Swim Test (FST) in mice. Additionally, SNP by itself produced no effect in the FST or in the openfield. This suggests indirectly a differential involvement of the nitrinergic system in the antidepressant vs. psychotomimetic effect of ketamine, although an influence of species-specific differences cannot be excluded in this interpretation.