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Comparative Clinical Pathology
Published in: Comparative Clinical Pathology 4/2017

01-07-2017 | Original Article

Nicorandil reverses the behavioral changes and brain oxidative stress in a model of schizophrenia induced by ketamine in mice

Authors: Omar M. E. Abdel-Salam, Marwa El-Sayed El-Shamarka

Published in: Comparative Clinical Pathology | Issue 4/2017

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Abstract

We examined the effect of the KATP channel opener nicorandil and the KATP channel blocker glibenclamide on the behavioral and biochemical responses to ketamine in mice. Ketamine was injected at 30 mg/kg intraperitoneally (i.p.) daily for 2 weeks, and mice were then treated with either saline, glibenclamide (5 mg/kg), nicorandil (1 or 5 mg/kg), sucrose 1 g/kg, or glibenclamide + sucrose 1 g/kg, i.p. daily for another 8 days. The control group received only saline. Data indicated that (i) ketamine increased locomotion, rearing, and grooming behaviors. Locomotor activity increased in the center while rearing activity increased in the periphery and center of the open field. Social interaction was markedly decreased by ketamine. Nicorandil at 1 mg/kg increased and at 5 mg/kg produced marked depression in ambulation in the center of the field and in rearing in the field periphery. Locomotor activity and rearing of ketamine-treated mice were not affected by glibenclamide. Meanwhile, either agent reversed the increase in grooming and the inhibition of social interaction caused by ketamine. Sucrose had no significant effect on grooming or social interaction of mice given ketamine but increased ambulation and rearing activity in the field center. (ii) Ketamine caused a significantly elevated brain lipid peroxidation (malondialdehyde) while decreasing reduced glutathione, nitric oxide, and paraoxonase-1 activity. These biochemical alterations were markedly alleviated by nicorandil or glibenclamide. The study suggests a potential therapeutic value for the KATP channel opener nicorandil in the ketamine model of schizophrenia.
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Metadata
Title
Nicorandil reverses the behavioral changes and brain oxidative stress in a model of schizophrenia induced by ketamine in mice
Authors
Omar M. E. Abdel-Salam
Marwa El-Sayed El-Shamarka
Publication date
01-07-2017
Publisher
Springer London
Published in
Comparative Clinical Pathology / Issue 4/2017
Print ISSN: 1618-5641
Electronic ISSN: 1618-565X
DOI
https://doi.org/10.1007/s00580-017-2471-x

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