期刊
EUROPEAN NEUROPSYCHOPHARMACOLOGY
卷 25, 期 10, 页码 1848-1852出版社
ELSEVIER
DOI: 10.1016/j.euroneuro.2015.06.012
关键词
NMDA receptor; Ketamine; Nitric oxide; Depression; Psychosis
资金
- Deutsche Forschungsgemeinschaft (DFG) [GA427/11-1, Sonderforschungsbereich (SFB) 636]
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 (0.5-1 mg/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 speciesspecific differences cannot be excluded in this interpretation. (C) 2015 Elsevier B.V. and ECNP. All rights reserved.
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