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Creatine attenuates seizure severity, anxiety and depressive-like behaviors in pentylenetetrazole kindled mice

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Abstract

Epilepsy has been associated with several behavioral changes such as depression and anxiety while some antiepileptic drugs can precipitate psychiatric conditions in patients. This study evaluated the ameliorative effect of creatine on seizure severity and behavioral changes in pentylenetetrazole (PTZ) kindled mice. Mice were kindled by administering sub-convulsive doses of PTZ (35 mg/kg i.p.) at interval of 48 h. The naïve group (n = 7) constituted group 1, while successfully kindled mice were randomly assigned to five groups (n = 7). Group II served as vehicle treated group; groups III-V were treated with creatine 75, 150, and 300 mg/kg/day, p.o; Group V was given 25 mg/kg/day of phenytoin p.o. The treatment was for 15 consecutive days. The intensity of convulsion was scored according to a seven-point scale ranging from stage 0–7. Tail suspension test (TST) and Elevated plus maze (EPM) were utilized to assess depression and anxiety-like behavior respectively. After behavioral evaluation on day 15th, their brain was isolated and assayed for catalase, superoxide dismutase, reduced glutathione, and malondialdehyde. There was a significant (p < 0.05) reduction in the seizure scores, anxiety and depression-like behaviors in mice from the 5th day of treatment. The antioxidant assays revealed significant (p < 0.05) increase in catalase and reduced glutathione, and significant (p < 0.05) reduction in lipid peroxidation in treated mice. This study provides evidence for the seizure reducing property of creatine and its ameliorating potential on anxiety and depressive-like behaviors that follows seizure episodes.

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Authors and Affiliations

  1. Department of Pharmacology & Toxicology, Prof Dora Akunyili College of Pharmacy, Igbinedion University Okada, Benin City, Edo, Nigeria

    Emmanuel O. Okwuofu, Akinpelu L. Abiola, Ighodaro Igbe & Ononiwu Chinazamoku

  2. Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Benin, 300001, Benin City, Nigeria

    Abigail M. Akhigbemen, Raymond I. Ozolua & Ighodaro Igbe

  3. Department of Biochemistry, Faculty of Science, Obafemi Awolowo University, Ile Ife, Osun, Nigeria

    Gbenga E. Ogundepo

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  1. Emmanuel O. Okwuofu
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  2. Gbenga E. Ogundepo
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  3. Abigail M. Akhigbemen
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Contributions

The study was conceived and designed by EOO and I.I; experiments and data acquisition were carried out by EOO, AAM, ALA,OGE and OC. Data analysis and manuscript preparation were undertaken by EOO,RIO, I.I and ALA. Editing and reduction were done by RIO. All the authors approve of the manuscript submission and accept responsibility for the entire content of this manuscript.

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Correspondence to Emmanuel O. Okwuofu.

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Okwuofu, E.O., Ogundepo, G.E., Akhigbemen, A.M. et al. Creatine attenuates seizure severity, anxiety and depressive-like behaviors in pentylenetetrazole kindled mice. Metab Brain Dis 36, 571–579 (2021). https://doi.org/10.1007/s11011-021-00684-w

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