title: The effect of topiramate on GABA(B) receptor, vesicular GABA transporter and paired-pulse inhibition in the gerbil hippocampus.
abstract: 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 (> or = 40 mg/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.
authors.affiliation: Department of Anatomy, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, South Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kwak
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Hui-Chul
authors.initials: HC
authors.lastname: Choi
authors.forename: Hong-Ki
authors.initials: HK
authors.lastname: Song
authors.forename: Yeong-In
authors.initials: YI
authors.lastname: Kim
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015153:Blotting, Western; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D005849:Gerbillinae; D007150:Immunohistochemistry; D009433:Neural Inhibition / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology; D000077236:Topiramate; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018755:GABA Agonists; D018696:Neuroprotective Agents; D018080:Receptors, GABA-B; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C493406:vesicular GABA transporter; D000077236:Topiramate; D005632:Fructose; D001418:Baclofen