Abstracts

RATIONALE: Kindling is generally thought to be the most useful model of temporal lobe epilepsy, i.e. the common and difficult-to-treat type of epilepsy. The PTZ-induced kindling model in rats has been widely used as an epilelptogenesis mechanism, which would change regional excitatory and inhibitory amino acid receptors. The anticonvulsant topiramate is effective in laboratory animals against maximal electroshock seizures, amygdala kindling, and spike-wave discharges and has demonstrated efficacy in humans for treatment of complex partial seizures. However, its mechanism of action in chemically induced seizure has yet to be clearly elucidated. This study was investigated to know one kind of the action mechanism of topiramate in PTZ kindled rat brain.METHODS: Male Wistar rats (n=19) were kindled by repeated administration, 5 times in a week, by an subconvulsant dose of PTZ(35 mg/kg). The kindling score was significantly increased after 6 injections and the definitive kindling score (more than 4 point) was gotten after 15 injections. In control group we injected normal saline intra peritoneally(n=4). After kindling was established, animals were divided into 4 subgroups; TPM-0(no topiramate medication), TPM-10(topiramate 10mg/kg p.o. 4 hour before PTZ injection), TPM-30(topiramate 30mg/kg p.o. 4 hour before PTZ injection), TPM-50(topiramate 50mg/kg p.o. 4 hour before PTZ injection). we investigated kindling scores and the changes of mRNA gene expression of GABA receptor alpha1 subunit.RESULTS: The kindling scores in TPM-30 and TPM-50 groups showed a significant decrease during TPM administration period. The percent changes of mRNA gene expression of GABA receptor alpha1 subunit after kindling were decreased to 58.1[plusminus]11.9%, 63.5[plusminus]8.9%, 72.2[plusminus]7.5% in hippocampus, amygdala, and basal ganglia respectively(TPM-0 subgroup). Although there was no significant difference, mRNA gene expression of GABA receptor alpha1 subunit during TPM medication period show the tendancy of returning to normal level.CONCLUSIONS: These result support the conclusion that GABA receptor alpha1 subunit may contribute to the development of PTZ-induced kindling. The anticonvulsant activity of topiramate might originate from the action to the GABA receptor alpha1 subunit but cannot be confirmed from this study.