Purpose: To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development.
Methods: Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures.
Results: In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation.
Conclusions: Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.