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Morin Attenuates Neurochemical Changes and Increased Oxidative/Nitrergic Stress in Brains of Mice Exposed to Ketamine: Prevention and Reversal of Schizophrenia-Like Symptoms

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Abstract

Previous studies have revealed that morin (MOR), a neuroactive bioflavonoid, with proven psychotropic and neuroprotective properties reduced schizophrenic-like behaviors in mice. This study further evaluated the ability of MOR to prevent and reverse ketamine-induced schizophrenic-like behaviors and the underlying neurochemical changes and increased oxidative/nitrergic stress in mice. In the preventive protocol, mice received intraperitoneal injection of MOR (100 mg/kg), reference antipsychotic drugs [haloperidol (1 mg/kg), risperidone (0.5 mg/kg)], or saline daily for 14 consecutive days prior to i.p. injection of ketamine (KET) (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or saline for 14 days prior to MOR, haloperidol, risperidone, or saline treatments. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction test) and cognitive (Y-maze test) symptoms were evaluated. Thereafter, the brain levels of dopamine, glutamate, 5-hydroxytryptamine and acetyl-cholinesterase, as well as biomarkers of oxidative/nitrergic stress were measured in the striatum, prefrontal-cortex (PFC) and hippocampus (HC). Morin prevented and reversed KET-induced hyperlocomotion, social and cognitive deficits. Also, MOR or risperidone attenuated altered dopaminergic, glutamatergic, 5-hydroxytryptaminergic and cholinergic neurotransmissions in brain region-dependent manner. The increased malondialdehyde and nitrite levels accompanied by decreased glutathione concentrations in the striatum, PFC and HC in KET-treated mice were significantly attenuated by MOR or risperidone. Taken together, these findings suggest that the anti-schizophrenic-like activity of MOR may be mediated via mechanisms related to attenuation of neurochemical changes and oxidative/nitrergic alterations in mice.

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Acknowledgements

The Authors are thankful to Dr. A. O. Odeseye and his colleagues of the Department of Microbiology and Biotechnology, Nigerian Institute of Science Laboratory Technology (NISLT) for his technical assistance during the enzyme immunoassay.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo state, Nigeria

    Benneth Ben-Azu, Adegbuyi Oladele Aderibigbe, Aya-Ebi Okubo Eneni, Abayomi Mayowa Ajayi & Solomon Umukoro

  2. Inflammation and Immunopharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo state, Nigeria

    Ezekiel O. Iwalewa

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  1. Benneth Ben-Azu
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All applicable international, national, and/or institutional (University of Ibadan Animal Care and Use Research Ethics Committee) guidelines for the care and use of animals were followed according to the ethical approval number: UI-ACUREC/App/12/2016/01.

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Ben-Azu, B., Aderibigbe, A.O., Eneni, AE.O. et al. Morin Attenuates Neurochemical Changes and Increased Oxidative/Nitrergic Stress in Brains of Mice Exposed to Ketamine: Prevention and Reversal of Schizophrenia-Like Symptoms. Neurochem Res 43, 1745–1755 (2018). https://doi.org/10.1007/s11064-018-2590-z

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