Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model

Purpose: To study anticonvulsive and antiepileptogenic effects of singe levetiracetam (LEV) administration in the model of audiogenic kindling. Methods: Rats of Krushinsky-Molodkina (KM) strain genetically susceptible to severe audiogenic seizures received one intraperitoneal injection of saline, low (6 mg/kg) or high (50 mg/kg) dose of LEV before or after audiogenic kindling. One hour postinjection, an audiogenic seizure was induced to assess anticonvulsive effect of LEV in nonkindled and kindled rats. To examine antiepileptogenic activity of LEV, nonkindled rats injected with the drug or saline were kindled with repeated sound stimulations. Audiogenic kindling development manifested in an appearance and progressive prolongation of an additional seizure phase, post-tonic-clonus. The latency and duration of audiogenic seizures and the duration of every seizure phase (running, tonic, post-tonic-clonic) were measured. Results: One hour posttreatment, LEV dose-dependently lengthened the latency and reduced the duration of audiogenic seizures in both nonkindled and kindled rats. The seizure shortening resulted from selective suppression of tonic and kindled post-tonic-clonic phases. The dose of 50 mg/kg completely blocked tonic and clonic convulsions 1 h postinjection. The anticonvulsive effect of LEV was more pronounced in kindled than in nonkindled rats. Single LEV injection in the dose of 50 mg/kg prior audiogenic kindling significantly suppressed subsequent kindling progression indicating profound antiepileptogenic potency of the drug. Conclusions: The present study shows that LEV exerts both short-lasting anticonvulsive effect on audiogenic seizures and very long-lasting antiepileptogenic effect on audiogenic kindling. Remarkably, a single injection of LEV is enough to significantly suppress kindling progression in KM rats.