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

Amini-Khoei H, H and Kordjazy N, N and Haj-Mirzaian A, A and Amiri S, S and Haj-Mirzaian A, A and Shirzadian A, A and Hasanvand A, A and Balali-Dehkordi S, S and Hassanipoor, M and Dehpour, AR (2018) Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor. Can J Physiol Pharmacol..

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/29558629

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 (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg). We found that inducible NOS inhibitor, aminoguanidine (100 mg/kg), had no effect on the anti-seizure 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 NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of sub-effective dose of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of nNOS 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 decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: sobhan rezaiian
Date Deposited: 08 Apr 2018 20:34
Last Modified: 08 Apr 2018 20:34
URI: http://eprints.lums.ac.ir/id/eprint/1215

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