Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor

(2018) Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor. Canadian Journal of Physiology and Pharmacology. pp. 742-750. ISSN 0008-4212

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Abstract

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-D-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor N-G-L-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDAreceptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

Item Type: Article
Keywords: minocycline anticonvulsant nitric oxide NO neuronal nitric oxide synthase nNOS N-methyl-D-aspartate NMDA social-isolation stress cerebellar granule cells forced swimming test status epilepticus nmda receptors in-vitro antiepileptic drugs hippocampal damage oxidative stress nitrergic system Pharmacology & Pharmacy Physiology
Page Range: pp. 742-750
Journal or Publication Title: Canadian Journal of Physiology and Pharmacology
Journal Index: ISI
Volume: 96
Number: 8
Identification Number: https://doi.org/10.1139/cjpp-2017-0673
ISSN: 0008-4212
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/4250

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