Anticonvulsant effects of carbamazepine on spontaneous seizures in rats with kainate-induced epilepsy: comparison of intraperitoneal injections with drug-in-food protocols.
OBJECTIVE
The present study evaluated the effectiveness of intraperitoneal (IP) injections and oral administration of carbamazepine (CBZ) in food on the frequency of spontaneous motor seizures in rats with kainate-induced epilepsy. The purpose was to develop a convenient drug-in-food approach for continuous, long-term administration of potential antiepileptic drugs (AEDs).


METHODS
Single IP injections of CBZ (10-100 mg/kg) were compared to vehicle injections via six AED-versus-vehicle tests using a repeated-measures, crossover protocol. Similar protocols were used with CBZ-containing or control food pellets.


RESULTS
CBZ significantly reduced motor seizure frequency at 30 and 100 mg/kg after single IP injections, and these doses completely blocked motor seizures during a 6-h postdrug epoch in 25% and 70% of the animals, respectively. Single administrations of 30 mg/kg and 100 mg/kg CBZ in food also significantly reduced motor seizures, and blocked seizures in 33% and 89% of the rats, respectively. CBZ administered in food three times per day (100 mg/kg x3 CBZ in food) continuously blocked nearly all motor seizures over a 5-day period, and completely suppressed motor seizures in 50% of the animals tested.


CONCLUSIONS
CBZ strongly suppresses spontaneous motor seizures, and single doses of CBZ in food are as effective as IP injections in rats with kainate-induced epilepsy. CBZ administered regularly in food continuously blocks nearly all motor seizures, and may provide a relatively simple method to test AEDs in chronic models of epilepsy.
Grabenstatter
Heidi L
HL
Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado 80523, USA.
Clark
Suzanne
S
Dudek
F Edward
FE
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*; D005527:Food, Fortified; D007274:Injections, Intraperitoneal; D007608:Kainic Acid; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000235:genetics / Q000517:prevention & control*
D000927:Anticonvulsants; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D002220:Carbamazepine; D007608:Kainic Acid