EFFECTS OF LAMOTRIGINE AND CONVENTIONAL ANTIEPILEPTIC DRUGS ON AMYGDALA-KINDLED AND HIPPOCAMPAL-KINDLED SEIZURES IN RATS

We investigated the anticonvulsant and adverse behavioral effects of l amotrigine (LTG), a novel antiepileptic drug (AED), as well as other c onventional AEDs on kindled seizures in rats. We also applied an antic onvulsive dose of LTG in vivo to rats in which the hippocampus had bee n subjected to long-term potentiation (LTP). LTG potently attenuated l imbic-kindled seizures in a dose-dependent fashion, at doses at which animals showed no adverse behavioral effects. LTG was effective in pre venting kindled seizures for up to 24 h after a single i.p. administra tion. The anticonvulsant effects of LTG were reversed when the stimulu s current was raised to two or three times the generalized seizure-tri ggering threshold. Among the AEDs examined, valproate and LTG were the only drugs that engendered a potent anticonvulsant effect without con comitant adverse behavioral effects. Although all of the other AEDs ex hibited anticonvulsant effects with various potencies, they produced a dverse effects such as sedation or motor ataxia. Furthermore, an antic onvulsant dose of LTG did not affect either the induction or maintenan ce of tetanus-induced LTP in the hippocampus. These results indicate t hat LTG potently suppresses limbic-kindled seizures by raising the sei zure triggering-threshold in the kindling focus at doses that do not a ffect LTP in the hippocampus. (C) 1998 Elsevier Science B.V. All right s reserved.