A decrease in seizure susceptibility to lidocaine in kindled epileptic rats

Lidocaine induces electroencephalographic seizures and generalized convulsions at large doses. It is possible that epileptic patients are more susceptible to the proconvulsant effect of lidocaine. Using a kindling model of epilepsy, we examined whether the seizure susceptibility to lidocaine increases in epileptic rats. Kindled epileptic rats were prepared by repeated, initially subconvulsive, electrical stimulations applied to the amygdala for 9-14 days through a chronically implanted electrode, resulting in the establishment of a long-lasting epileptic focus. Unexpectedly, kindled rats had significantly less susceptibility to the proconvulsant action of IV lidocaine. Lidocaine-induced convulsions were observed in 11%, 75%, and 77% of control 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 manner. We conclude that the critical mechanisms underlying lidocaine-induced seizures differ from the mechanisms underlying kindled epileptogenesis. Furthermore, the establishment of a kindled epileptic focus decreases susceptibility to the proconvulsant action of lidocaine.