title: Nitroprusside single-dose prevents the psychosis-like behavior induced by ketamine in rats for up to one week.
abstract: Recently, we found a rapid and long-lasting improvement of symptoms in schizophrenic patients on antipsychotics after a single four-hour infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor with a short half-life. This improvement persisted for up to 4weeks. Because these patients remained on antipsychotics after infusion of SNP was finished, the question arises about whether this improvement was due to SNP itself. We have now investigated whether SNP, alone, can produce preventive antipsychotic effects in rats treated with ketamine (KET). 56 adult rats divided into 7 groups were infused with SNP 4mg/kg, KET 25mg/kg, or saline as follows: group1 - saline, group2 - SNP, group3 - KET, group4 - KET 12h after SNP, group5 - KET 1day after SNP, group6 - KET 2days after SNP, and group7 - KET 1week after SNP. The animals were filmed in an open field arena for 30min and the videos were later analyzed by ANY-Maze software to measure activity and stereotypy. SNP significantly prevented the emergence of hyperactivity induced by KET when it was administered for up to 1week before KET, and prevented the emergence of stereotypies when it was administered for up to 1day before KET. These findings in rats, which have an even faster metabolic rate than humans, suggest that the long-lasting effects observed in our clinical trial with SNP in humans could have been due to SNP itself, and indicate for the first time that SNP may present preventive antipsychotic effects.
authors.affiliation: Department of Neuroscience and Behavioral Science, University of Sao Paulo (USP) - Ribeirao Preto, SP CEP 14048-900, Brazil; Department of Clinical Medicine, Federal University of Rio Grande do Norte, Natal, RN CEP 59012420, Brazil. Electronic address: j.p@usp.br.
authors.forename: Joao Paulo
authors.initials: JP
authors.lastname: Maia-de-Oliveira
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, RN, CEP 59012420, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lobão-Soares
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, RN, CEP 59012420, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Ramalho
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, RN, CEP 59012420, Brazil.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, RN, CEP 59012420, Brazil.
authors.forename: Vanessa Paula
authors.initials: VP
authors.lastname: Soares
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, RN, CEP 59012420, Brazil.
authors.forename: Leslie
authors.initials: L
authors.lastname: Teixeira
authors.affiliation: Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 12-105B CSB, Edmonton, AB T6G 2G3, Canada.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.affiliation: Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 12-105B CSB, Edmonton, AB T6G 2G3, Canada.
authors.forename: Serdar M
authors.initials: SM
authors.lastname: Dursun
authors.affiliation: Department of Neuroscience and Behavioral Science, University of Sao Paulo (USP) - Ribeirao Preto, SP CEP 14048-900, Brazil.
authors.forename: Jaime E C
authors.initials: JE
authors.lastname: Hallak
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007649:Ketamine; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D009599:Nitroprusside / Q000008:administration & dosage*; D011618:Psychotic Disorders / Q000503:physiopathology / Q000517:prevention & control*; D011897:Random Allocation; D017208:Rats, Wistar; D012399:Rotation; D012984:Software; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014741:Video Recording
chemical_list: D014150:Antipsychotic Agents; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D007649:Ketamine
keywords: Ketamine; Nitric oxide; Schizophrenia; Sodium nitroprusside