Opposite effects of GABA(B) receptor antagonists on absences and convulsive seizures

被引:113
作者
Vergnes, M
Boehrer, A
Simler, S
Bernasconi, R
Marescaux, C
机构
[1] Unité INSERM 398, Fac. de Med., 11 Rue Humann
关键词
epilepsy; cortex; hippocampus; thalamus; c-Fos; GABAB receptor antagonist;
D O I
10.1016/S0014-2999(97)01085-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In Wistar rats with spontaneous non-convulsive absence epilepsy, absence seizures were dose dependently suppressed by intraperitoneal administration of the GABA(B) receptor antagonists CGP 36742, 50-400 mg/kg, and CGP 56999, 0.25-0.75 mg/kg, and by bilateral microinjections of the same compounds into the lateral nuclei of the thalamus. In rats susceptible to audiogenic seizures, intraperitoneal administration of both GABA(B) receptor antagonists, at doses which suppressed absence seizures, facilitated the elicitation of sound-induced tonic seizures. In non-epileptic control rats, intraperitoneal injections of higher doses of CGP 36742 (800-2400 mg/kg) and CGP 56999 (3-6 mg/kg) induced delayed clonic convulsions, which were suppressed by pretreatment with baclofen. c-Fos protein was expressed after GABA(B) receptor antagonist-induced seizures in the cortex, hippocampus, amygdala, perirhinal and piriform cortex. Intra-cortical and hippocampal microinfusion of both GABA(B) receptor antagonists produced focal seizures. In conclusion, GABA(B) receptor antagonists suppress non-convulsive absence seizures by blocking thalamic GABA(B) receptors, while they induce convulsions in cortical and limbic structures. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:245 / 255
页数:11
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