In the present study, we investigated the effects of melatonin on penicillin-induced epileptiform activity in female Wistar rats. The left cereoral cortex was exposed by craniotomy under urethane anesthesia for the induction of epilepsy by intracortical microinjection of penicillin (200 IU) into the left sensorimotor cortex. The epileptiform activity was analyzed by electrocorticogram (ECoG). Ten minutes before the penicillin injection, 20, 40 or 80 mu g of melatonin was administered intracerebroventricularly and ECoG was monitored for 1 h. Forty or 80 mu g of melatonin significantly increased the latency to epileptiform activity. Furthermore, melatonin significantly decreased the frequency of spike and spike-wave activity, whereas the amplitude of spikes remained unchanged. In conclusion, data obtained from the present study suggest that melatonin suppresses penicillin-induced epileptiform activity, and it may be an endogenous anticonvulsant. (c) 2006 Elsevier B.V. All rights reserved.