title: Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia.
abstract: BACKGROUND
  Better treatments for schizophrenia are urgently needed. The therapeutic use of the nitric oxide (NO)-donor sodium nitroprusside (SNP) in patients with schizophrenia has shown promising results. The role of NO in schizophrenia is still unclear, and NO modulation is unexplored in ketamine (KET) animal models to date. In the present study, we compared the behavioral effects of pre- and post-treatment with SNP, glyceryl trinitrate (GTN), and methylene blue (MB) in the acute KET animal model of schizophrenia. The present study was designed to test whether acute SNP, GTN, and MB treatment taken after (therapeutic effect) or before (preventive effect) a single KET injection would influence the behavior of rats in the sucrose preference test, object recognition task and open field.
  
  
  RESULTS
  The results showed that KET induced cognitive deficits and hyperlocomotion. Long- term memory improvement was seen with the therapeutic GTN and SNP treatment, but not with the preventive one. MB pretreatment resulted in long-term memory recovery. GTN pre-, but not post-treatment, tended to increase vertical and horizontal activity in the KET model. Therapeutic and preventive SNP treatment consistently decreased KET-induced hyperlocomotion.
  
  
  CONCLUSIONS
  NO donors - especially SNP - are promising new pharmacological candidates in the treatment of schizophrenia. In addition, we showed that the potential impact of NO-related compounds on KET-induced behavioral changes may depend on the temporal window of drug administration.
authors.affiliation: Department of Neurosciences and Behavior, Ribeirao Preto School of Medicine, University of Sao Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, Brazil. ludykandra@gmail.com.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Ribeirao Preto, Brazil. ludykandra@gmail.com.
authors.forename: Ludmyla
authors.initials: L
authors.lastname: Kandratavicius
authors.affiliation: Department of Neurosciences and Behavior, Ribeirao Preto School of Medicine, University of Sao Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, Brazil. priscila.abi@gmail.com.
authors.forename: Priscila Alves
authors.initials: PA
authors.lastname: Balista
authors.affiliation: Department of Neurosciences and Behavior, Ribeirao Preto School of Medicine, University of Sao Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, Brazil. daniwolf.usp@gmail.com.
authors.forename: Daniele Cristina
authors.initials: DC
authors.lastname: Wolf
authors.affiliation: Department of Biomechanics, Ribeirao Preto School of Medicine, Medicine and Rehabilitation, USP, Ribeirao Preto, Brazil. joaoabrao@fmrp.usp.br.
authors.forename: Joao
authors.initials: J
authors.lastname: Abrao
authors.affiliation: Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, USP, Ribeirao Preto, Brazil. prbevora@gmail.com.
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Evora
authors.affiliation: Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, USP, Ribeirao Preto, Brazil. alfredo@fmrp.usp.br.
authors.forename: Alfredo Jose
authors.initials: AJ
authors.lastname: Rodrigues
authors.affiliation: Department of Neurosciences and Behavior, Ribeirao Preto School of Medicine, University of Sao Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, Brazil. crischaves01@yahoo.com.br.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chaves
authors.affiliation: Brain Institute, Universidade Federal do Rio Grande do Norte, Natal, Brazil. j.p@usp.br.
authors.forename: Joao Paulo
authors.initials: JP
authors.lastname: Maia-de-Oliveira
authors.affiliation: Department of Neurosciences and Behavior, Ribeirao Preto School of Medicine, University of Sao Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, Brazil. jpleite@fmrp.usp.br.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Ribeirao Preto, Brazil. jpleite@fmrp.usp.br.
authors.forename: Joao Pereira
authors.initials: JP
authors.lastname: Leite
authors.affiliation: Department of Psychiatry (NRU), University of Alberta, Edmonton, Alberta, Canada. dursun@ualberta.ca.
authors.forename: Serdar Murat
authors.initials: SM
authors.lastname: Dursun
authors.affiliation: Department of Psychiatry (NRU), University of Alberta, Edmonton, Alberta, Canada. glen.baker@ualberta.ca.
authors.forename: Glen Bryan
authors.initials: GB
authors.lastname: Baker
authors.affiliation: Department of Pharmacology, Ribeirao Preto School of Medicine, USP, Ribeirao Preto, Brazil. fsguimar@fmrp.usp.br.
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimaraes
authors.affiliation: Department of Neurosciences and Behavior, Ribeirao Preto School of Medicine, University of Sao Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, Brazil. jhallak@fmrp.usp.br.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Ribeirao Preto, Brazil. jhallak@fmrp.usp.br.|National Institute of Science and Technology in Translational Medicine (INCT-TM - CNPq), Ribeirao Preto, Brazil. jhallak@fmrp.usp.br.
authors.forename: Jaime Eduardo Cecilio
authors.initials: JE
authors.lastname: Hallak
mesh_terms: D000208:Acute Disease; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D009043:Motor Activity; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D055697:Taste Perception / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D019422:Dietary Sucrose; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D005996:Nitroglycerin; D008751:Methylene Blue