The effect of topiramate on GABA(B) 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 (> 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.
Kim
Duk-Soo
DS
Department of Anatomy, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, South Korea.
Kwak
Sung-Eun
SE
Kim
Ji-Eun
JE
Won
Moo-Ho
MH
Choi
Hui-Chul
HC
Song
Hong-Ki
HK
Kim
Yeong-In
YI
Choi
Soo-Young
SY
Kang
Tae-Cheon
TC
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
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