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: Duk-Soo Kim, Sung-Eun Kwak, Ji-Eun Kim, Moo-Ho Won, Hui-Chul Choi, Hong-Ki Song, Yeong-In Kim, Soo-Young Choi, Tae-Cheon Kang
• Journal: Neuroscience research (Neurosci Res) Vol. 53 Issue 4 Pg. 413-20 (Dec 2005) ISSN: 0168-0102 [Print] Ireland
• PMID: 16207499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GABA Agonists
• Neuroprotective Agents
• Receptors, GABA-B
• Vesicular Inhibitory Amino Acid Transport Proteins
• vesicular GABA transporter
• Topiramate
• Fructose
• Baclofen

Topics

• Animals
• Baclofen (pharmacology)
• Blotting, Western
• Dentate Gyrus (drug effects, metabolism)
• Excitatory Postsynaptic Potentials (drug effects)
• Fructose (analogs & derivatives, pharmacology)
• GABA Agonists (pharmacology)
• Gerbillinae
• Immunohistochemistry
• Neural Inhibition (drug effects)
• Neuroprotective Agents (pharmacology)
• Receptors, GABA-B (drug effects, metabolism)
• Seizures (physiopathology)
• Topiramate
• Vesicular Inhibitory Amino Acid Transport Proteins (drug effects, metabolism)