Abstracts

To extend our understanding of the properties of topiramate (TPM), we investigated the effect of TPM on GABA[sub]B[/sub] receptor systems in the dentate gyrus of gerbil. Following TPM or baclofen treatment, we investigated changes in paired-pulse responses in the gerbil hippocampus. In addition, alterations in GABA[sub]B[/sub] receptor subunit immunoreactivity and vesicular GABA transporter (VGAT) immunoreactivity in the gerbil hippocampus were examined by immunohistochemical and immunoblot methods. TPM treatment ([ge] 40 mg/kg) dramatically decreased GABA[sub]B[/sub]R2, not GABA[sub]B[/sub]R1, immunoreactivity in hilar interneurons as compared with saline treated animals, although its immunoreactivity in principal neurons remained. Both GABA[sub]B[/sub] receptor subunit immunoreactivities were unaffected by low TPM dosages ([lt] 40 mg/kg). TPM treatment ([ge] 40 mg/kg) also increased vesicular GABA transporter immunoreactivity in the dentate gyrus. Following TPM treatment ([ge] 40 mg/kg), the paired-pulse facilitation in the dentate gyrus was markedly reduced, which was unaffected by baclofen co-treatment. These findings suggest that TPM enhanced the paired pulse inhibition in the dentate gyrus of gerbils by down-regulation of GABA[sub]B[/sub] receptor expression on interneurons. Therefore, these properties of TPM may be another possible antiepileptic effect, which plays an important role in preventing the spread of seizure activity without proconvulsant effects.