The anticonvulsant activity of cannabinoids (CB) has been shown to be exerted through the CB1 receptor activation. Aim of this study was to evaluate the protective effect of (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN 55,212-2, CB agonist) alone or in combination with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methy l-1H-pyrazole-3-carboxamide (AM251, selective CB1 antagonist) in an in vivo experimental model of temporal lobe epilepsy (maximal dentate gyrus activation - MDA) in the rat. The significative anticonvulsant effect of WIN 55,212-2 (21 mg kg-1) was dramatically reduced by pre-treatment with AM251 (1 mg kg-1, 30 min interval). Nevertheless, in an experimental model per se not inducing a basal activation of CB1 receptors, AM251, when administered alone at the same dose, did not alter the number of DG responses to the AB stimulation nor the severity of MDA events. Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of temporal lobe epilepsy. Moreover, the partial suppression of WIN 55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise an antiepileptic effect exerted by WIN 55,212-2 strictly linked to an increased CB1 receptor activation or to the functional involvement of an alternative receptor subtype.