Leptin is an adipose tissue-derived peptide hormone, which acts as a satiety factor to reduce appetite by interactions with hypothalamic neurons. The other possible physiological functions of leptin are still unclear. In this study, we have evaluated dose-dependent effect of leptin on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorymotor cortex. Thirty minutes after penicillin injection, 1, 2 or 10 mu g of leptin was administrated intracerebroventricularly (i.c.v.). Leptin (1, 2 or 10 mu g) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. One or two micrograms of leptin significantly increased the frequency of epileptiform activity in the penicillin-pretreated animals. The high dose of leptin (10 mu g) did not significantly change either amplitude or frequency of epileptiform activity. One microgram i.c.v. leptin was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The proconvulsant effects of leptin appeared 90 min after leptin (I and 2 jig) injection. These data indicate that leptin increases the frequency of penicillin-induced epileptic activity. We speculate that this action of leptin might suggest that leptin may be a proconvulsant substance. 2005 Elsevier Inc. All rights reserved.