Effects of Vigabatrin on Pilocarpine-Induced Seizures in Immature Rats

Choe, Bo Ram; Lee, In Goo; Whang, Kyung Tae

Abstract

PURPOSE: Vigabatrin is a widely used antiepileptic drug that greatly increases whole brain gamma- aminobutyric acid(GABA). But little is known about the anticonvulsant effect of vigabatrin on pilocarpine-induced seizures in the immature rats. This study was conducted to determine the effects of vigabatrin on pilocarpine-induced seizures in the immature rats.
METHODS
Six to eight day old Sprague-Dawley rats were classified into control(n=5) and vigabatrin-treated(n=5) groups that were pretreated with 30mg/kg of vigabatrin. Animals received vigabatrin or saline, intraperitonealy, for 6 days, once a day. And on the 5th day, right and left cortical electrodes were placed in 10-14 day old animals using stereotaxic instrument. The following day 2.5-hour EEG recordings were obtained to monitor the latency to first electrographic seizures and to first status epilepticus induced by intraperitoneal injection of pilocarpine(200mg/kg). Data were analyzed using the log-rank test.
RESULTS
Electrographic seizures and status epilepticus were seen in 80% of vigabatrin-treated group, and in 100% of control group rats. And the latency to first seizure was 8.8+/-2.0 minutes in control group and 20.5+/-5.2 minutes in vigabatrin-treated animals(P<0.02), and to status epilepticus was 12.2+/-1.2 minutes in control group and 29.3+/-6.3 minutes in vigabatrin-treated group(P<0.03).
CONCLUSION
It was confirmed that 30mg/kg of vigabatrin administration for 6 days did not affect the body weight gain and behavior of immature rats and had an anticonvulsant effect. These findings might demonstrate that the prolonged latency to seizure, and to status epilepticus, was a time to reduce GABA that was elevated in the brain by vigabatrin administration below the seizure threshold, by pilocarpine.