Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.
OBJECTIVE
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.
Mazarati
Andréy
A
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752, USA.
Shin
Don
D
Auvin
Stéphane
S
Sankar
Raman
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004827:Epilepsy / Q000139:chemically induced* / Q000517:prevention & control*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control; D013997:Time Factors; D000077236:Topiramate
D000927:Anticonvulsants; D014677:Pharmaceutical Vehicles; D000077236:Topiramate; D005632:Fructose