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BMC Neurosci. 2015 Mar 7;16:9. doi: 10.1186/s12868-015-0149-3.

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

Author information

1
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.
2
Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Ribeirao Preto, Brazil. ludykandra@gmail.com.
3
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.
4
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.
5
Department of Biomechanics, Ribeirao Preto School of Medicine, Medicine and Rehabilitation, USP, Ribeirao Preto, Brazil. joaoabrao@fmrp.usp.br.
6
Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, USP, Ribeirao Preto, Brazil. prbevora@gmail.com.
7
Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, USP, Ribeirao Preto, Brazil. alfredo@fmrp.usp.br.
8
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.
9
Brain Institute, Universidade Federal do Rio Grande do Norte, Natal, Brazil. j.p@usp.br.
10
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.
11
Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Ribeirao Preto, Brazil. jpleite@fmrp.usp.br.
12
Department of Psychiatry (NRU), University of Alberta, Edmonton, Alberta, Canada. dursun@ualberta.ca.
13
Department of Psychiatry (NRU), University of Alberta, Edmonton, Alberta, Canada. glen.baker@ualberta.ca.
14
Department of Pharmacology, Ribeirao Preto School of Medicine, USP, Ribeirao Preto, Brazil. fsguimar@fmrp.usp.br.
15
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.
16
Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Ribeirao Preto, Brazil. jhallak@fmrp.usp.br.
17
National Institute of Science and Technology in Translational Medicine (INCT-TM - CNPq), Ribeirao Preto, Brazil. jhallak@fmrp.usp.br.

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.

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.

PMID:
25887360
PMCID:
PMC4354998
DOI:
10.1186/s12868-015-0149-3
[Indexed for MEDLINE]
Free PMC Article
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