Anticonvulsant and neurotoxic effects of intracerebroventricular injectionof phenytoin, phenobarbital and carbamazepine in an amygdala-kindling model of epilepsy in the rat

Objective: To determine the feasibility of the intracerebroventricular inje ction of phenytoin (PHT), phenobarbital (PB) and carbamazepine (CBZ) to con trol seizures in the amygdala kindling model in the rat, and also to determ ine the associated neurotoxic effects. Methods: Different doses of PHT (500 and 1250 mu l), PB (200, 500 and 1000 mu l) and CBZ (200 and 500 mu l) wer e injected intracerebroventricularly into amygdala kindled male Wistar rats . Seizures were induced with a fixed suprathreshold stimulus of 500 mu A at times between 15 and 60 min after the injection. Seizure intensity (Racine 's scale), latency, seizure duration and afterdischarge duration were measu red. Neurotoxicity was tested using ataxia and sedation scales and also usi ng a rotorod. Results: PB was found to be the most powerful anticonvulsant, and both PB and CBZ caused significant reductions in seizure intensity to less than stage 3 with the doses tested. PHT only reduced seizures for the first 15-30 min after application. PB was also the most toxic drug: followe d by CBZ and by PHT. Neurotoxicity was acceptable except in the cases of th e highest doses during the earliest periods tested. There was no mortality due to the injection of any of the drugs at the doses employed. Conclusions : The intracerebroventricular route is a feasible way to administer anticon vulsant drugs for seizure control in the kindling model. (C) 1999 Elsevier Science B.V. All rights reserved.