Mariana C Diana1,2, Fernanda F Peres1,2, Veronica Justi1,2, Rodrigo A Bressan3, Acioly L T Lacerda2,3, José Alexandre Crippa2,4, Jaime E C Hallak2,4, Vanesssa Costhek Abilio1,2. 1. Behavioral Neuroscience Laboratory, Department of Pharmacology, Federal University of São Paulo, São Paulo, Brazil. 2. National Institute for Translational Medicine (INCT-TM, CNPq/FAPESP/CAPES), Ribeirão Preto, Brazil. 3. LiNC-Laboratório Interdisciplinar de Neurociências Clínicas, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil. 4. Department of Neurosciences and Behaviour, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Abstract
AIMS: The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensive rats (SHR) strain. METHODS: Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. RESULTS: Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. CONCLUSION: Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia.
AIMS: The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensiverats (SHR) strain. METHODS:Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. RESULTS: Spontaneously hypertensiverats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. CONCLUSION: Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia.
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Authors: Mariana C Diana; Fernanda F Peres; Veronica Justi; Rodrigo A Bressan; Acioly L T Lacerda; José Alexandre Crippa; Jaime E C Hallak; Vanesssa Costhek Abilio Journal: CNS Neurosci Ther Date: 2018-04-14 Impact factor: 5.243
Authors: Fernanda F Peres; Mariana C Diana; Raquel Levin; Mayra A Suiama; Valéria Almeida; Ana M Vendramini; Camila M Santos; Antônio W Zuardi; Jaime E C Hallak; José A Crippa; Vanessa C Abílio Journal: Front Pharmacol Date: 2018-08-21 Impact factor: 5.810