title: Role of the nitric oxide donor sodium nitroprusside in the antidepressant effect of ketamine in mice.
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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Vogt
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Vogel
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Natascha
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Germany. Electronic address: Dragos.Inta@zi-mannheim.de.
authors.forename: Dragos
authors.initials: D
authors.lastname: Inta
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D007649:Ketamine; D010622:Phencyclidine
keywords: Depression; Ketamine; NMDA receptor; Nitric oxide; Psychosis