The effect of topiramate on GABAB receptor, vesicular GABA transporter and paired-pulse inhibition in the gerbil hippocampus

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 (≥ 40 mg/kg) dramatically decreased GABABR2, not GABABR1, 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 GABAB 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.