To extend our understanding of the properties of topiramate (TPM), we investigated the effect of TPM on GABAergic transmission in the dentate gyrus of gerbil. TPM treatment (≥ 40mg/kg) dramatically decreased GABA B R2, not GABA B R1, immunoreactivity in hilar interneurons. In contrast, TPM treatment increased vesicular GABA transporter immunoreactivity and the paired-pulse inhibition in the dentate gyrus of seizure prone gerbils. Furthermore, TPM effectively prevented the reduction of paired-pulse inhibition induced by baclofen treatment. These findings suggest that TPM may enhance GABA release in the dentate gyrus of gerbils by down-regulation of GABA B autoreceptor expression. Therefore, these properties of TPM may be another possible antiepileptic effect, which plays an important role in preventing the spread of seizure activity without proconvulsive effects.