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

Abstract

To determine the feasibility of the intracerebroventricular injection of phenytoin (PHT), phenobarbital (PB) and carbamazepine (CBZ) to control seizures in the amygdala kindling model in the rat, and also to determine the associated neurotoxic effects. Different doses of PHT (500 and 1250 microl), PB (200, 500 and 1000 microl) and CBZ (200 and 500 microl) were injected intracerebroventricularly into amygdala kindled male Wistar rats. Seizures were induced with a fixed suprathreshold stimulus of 500 microA at times between 15 and 60 min after the injection. Seizure intensity (Racine's scale), latency, seizure duration and afterdischarge duration were measured. Neurotoxicity was tested using ataxia and sedation scales and also using a rotorod. 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, followed by CBZ and by PHT. Neurotoxicity was acceptable except in the cases of the highest doses during the earliest periods tested. There was no mortality due to the injection of any of the drugs at the doses employed. The intracerebroventricular route is a feasible way to administer anticonvulsant drugs for seizure control in the kindling model.