To investigate the nitric oxide (NO) implication and GABA modulation of the epileptogenesis, we used the "maximal dentate gyrus activation" (MDA) model, comparable to human temporal lobe epilepsy. Rats were treated with vigabatrin (VGB: gamma-vinyl GABA) a selective inhibitor of GABA breakdown by GABA transaminase and of GABA transporter isoform 1 (GAT1). Intraperitoneal (i.p.) administration of 7-Nitroindazole (7-NI, a prevalent inhibitor of neuronal NO synthase, 50 mg/Kg i.p.) or L-Arginine (a precursor of NO synthesis, 1 g/Kg i.p.) were performed to elucidate the effects of NO manipulation either in control rats or in rats pre-treated with VGB (750 mg/Kg i.p.). The parameters studied in the MDA epilepsy model were: the time of onset of MDA, the duration of MDA and of the afterdischarge (AD). VGB acute administration induced a decrease of time of onset and an increase of MDA and AD duration. This response was probably due to an early effect of increased GABA-ergic inhibitory tone on autoreceptors. The proconvulsant effects of i.p. administration of L-Arginine on the parameters of the MDA model were unchanged in VGB-treated animals. On the contrary, the VGB- 7-NI coadministration failed to induce significant modification of MDA parameters except for a paradoxically increase of AD duration. The experimental data show the possible implication of NO/GABA system on the MDA model of seizures.