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
