Effects of intracortical microinjection of vitamin B12 on penicillin-induced epileptiform activity in rats

There are increasing studies indicating neuroprotective effects for vitamin B12. In the present study, the effect of intracortical microinjection of vitamin B12 was investigated on penicillin-induced epileptiform activity. We also examined the effects of intracortical microinjection of diazepam (a GABA-benzodiazepine receptor agonist) and flumazenil (a GABAbenzodiazepine receptor antagonist) to clarify the possible mechanism of vitamin B12. In urethane-anesthetized rats, epileptiform activity was induced by intracortical microinjection of penicillin (300 IU, 1.5 microL), and the number and amplitude of spike waves were analyzed using electroencephalographic (EEG) recordings. Intracortical microinjections of vitamin B12 at doses of 100 and 200 ng/site, diazepam at a dose of 200 ng/site and their ineffective doses (50 ng/site of vitamin B12 with 50 ng/site of diazepam) co-microinjection treatment significantly (P less than 0.05) reduced both the number and amplitude of spike waves. In addition, combined microinjection of effective doses of vitamin B12 (100 ng/site) and diazepam (200 ng/site) produced more antiepileptiform effect in comparison with their alone used doses. The antiepileptic effects induced by microinjection of vitamin B12 and diazepam at a same dose of 200 ng/site were prevented by the same site microinjection of 50 ng/site of flumazenil. The results showed antiepileptiform activities for vitamin B12 and diazepam AT the cerebral cortex level. A central GABA-benzodiazepine receptor complex-mediated mechanism might be involved in the antiepileptiform activity of vitamin B12.