Effects of topiramate on seizure susceptibility in kainate-kindled rats: involvement of peripheral-type benzodiazepine receptors.
This study was aimed to quantitatively evaluate the effects of topiramate (TPM) on seizure susceptibility and hippocampal peripheral-type benzodiazepine receptors (PBRs) in the kainic acid (KA) model of temporal lobe epilepsy. Male rats were randomized into saline control group, KA group, KA/TPM low dose group and KA/TPM high dose group. Three weeks after single injection of KA (10 mg kg(-1), sc), the effects of TPM were tested at two doses (10 and 30 mg kg(-1), sc) once a day for 1 week in KA/TPM low dose group or KA/TPM high dose group, respectively. Rats in KA group received comparable injections of saline. Four weeks after initial KA injection, a subconvulsant dose KA (5 mg kg(-1), sc) was administered in rats in these three groups. Rats in saline control group received equal volume of saline. All animals were decapitated and hippocampus synaptosomes were purified 180 min after behavioral observation. PBRs specific binding sites were assessed by an in vitro binding technique utilizing the highly selective ligand [(3)H]PK11195. Seizure threshold was elevated and specific PBRs binding in hippocampus was decreased by TPM in dose-dependent manner. Specific PBRs binding in hippocampus was significantly related to seizure latency and seizure intensity. These results suggest that TPM can reduce the susceptibility to seizures in KA-kindled rats and its anticonvulsant effect seems resulting from, at least in part, the reduced PBRs binding after treatment. These results also support the hypothesis that PBRs represent a novel target for antiepileptic drug development.
Chen
Chunfu
C
Department of Neurology, Shandong Provincial Hospital, 324 Jing 5 Wei 7 Road, Jinan 250021, China. chencf301@163.com
Lang
Senyang
S
Xu
Gelin
G
Liu
Xinfeng
X
Zuo
Pingping
P
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007202:Indicators and Reagents; D007546:Isoquinolines; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D017933:Peripheral Nervous System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D000077236:Topiramate
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D007202:Indicators and Reagents; D007546:Isoquinolines; D011963:Receptors, GABA-A; D000077236:Topiramate; D005632:Fructose; D007608:Kainic Acid; C037850:PK 11195