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

Amini-Khoei, Hossein and Kordjazy, Nastaran and Haj-Mirzaian, Arvin and Amiri, Shayan and Haj-Mirzaian, Arya and Shirzadian, Armin and Hasanvand, Amin and Balali-Dehkordi, Shima and Hassanipour, Mahsa and Dehpour, Ahmad Reza (2017) Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor. Can. J. Physiol. Pharmacol.

[img]
Preview
Text
Anticonvulsant effect of minocycline.pdf

Download (1MB) | Preview

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 NG-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
Uncontrolled Keywords: minocycline, anticonvulsant, nitric oxide, NO, neuronal nitric oxide synthase, nNOS, N-methyl-D-aspartate, NMDA
Subjects: QT physiology
QV pharmacology > QV 704 Pharmaceutics
Divisions: Reserach Vice-Chancellar Department > Advanced Herbal Medicine
Depositing User: Unnamed user with email nazari@skums.ac.ir
Date Deposited: 11 Sep 2018 09:32
Last Modified: 11 Sep 2018 09:32
URI: http://eprints.skums.ac.ir/id/eprint/7127

Actions (login required)

View Item View Item