A decrease in seizure susceptibility to lidocaine in kindled epileptic rats

Lidocaine induces electroencephalographic seizures and generalized convulsi ons at large doses. It is possible that epileptic patients are more suscept ible to the proconvulsant effect of lidocaine. Using a kindling model of ep ilepsy, we examined whether the seizure susceptibility to lidocaine increas es in epileptic rats. Kindled epileptic rats were prepared by repeated, ini tially subconvulsive, electrical stimulations applied to the amygdala for 9 -14 days through a chronically implanted electrode, resulting in the establ ishment of a long-lasting epileptic focus. Unexpectedly, kindled rats had s ignificantly less susceptibility to the proconvulsant action of IV lidocain e, Lidocaine-induced convulsions were observed in 11%, 75%, and 77% of cont rol rats at 7.5, 10.0, and 12.5 mg/kg, respectively, compared with 0%, 25%, and 37% of amygdala-kindled rats, respectively. We also demonstrated that small doses of lidocaine suppressed kindled seizures in a dose-dependent ma nner. We conclude that the critical mechanisms underlying lidocaine-induced seizures differ from the mechanisms underlying kindled epileptogenesis. Fu rthermore, the establishment of a kindled epileptic focus decreases suscept ibility to the proconvulsant action of lidocaine.