Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia

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Kandratavicius, Ludmyla ^{[1, 2]} ; Balista, Priscila Alves ^[1] ; Wolf, Daniele Cristina ^[1] ; Abrao, Joao ^[3] ; Evora, Paulo Roberto ^[4] ; Rodrigues, Alfredo Jose ^[4] ; Chaves, Cristiano ^[1] ; Maia-de-Oliveira, Joao Paulo ^[5] ; Leite, Joao Pereira ^{[1, 2]} ; Dursun, Serdar Murat ^[6] ; Baker, Glen Bryan ^[6] ; Guimaraes, Francisco Silveira ^[7] ; Cecilio Hallak, Jaime Eduardo ^{[1, 2, 8]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Neurosci & Behav, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14049900 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Dept Biomech, Ribeirao Preto Sch Med Med & Rehabil, BR-14049900 Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Dept Surg & Anat, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto - Brazil

^[5] Univ Fed Rio Grande do Norte, Inst Brain, BR-59072970 Natal, RN - Brazil

^[6] Univ Alberta, Dept Psychiat NRU, Edmonton, AB - Canada

^[7] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto - Brazil

^[8] CNPq, INCT TM, Natl Inst Sci & Technol Translat Med, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC NEUROSCIENCE; v. 16, MAR 7 2015.
• Citações Web of Science: 17

Resumo

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. Conclusion: 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. (AU)

• Processo FAPESP: 05/56447-7 - Pesquisa através de imagens por ressonância magnética de alto campo destinadas a estudos em humanos
• Beneficiário: João Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Programa CINAPCE - Temático