The selective GABA(B) antagonist CGP-35348 blocks spike-wave bursts in the cholesterol synthesis rat absence epilepsy model

被引:39
作者
Smith, KA
Fisher, RS
机构
[1] MED CTR,PHOENIX,AZ 85013
[2] ST JOSEPHS HOSP,BARROW NEUROL INST,DEPT NEUROL,PHOENIX,AZ 85013
关键词
epilepsy; seizure; absence; Petit mal; gamma-aminobutyric acid; electroencephalography; pharmacological antagonist; rat;
D O I
10.1016/0006-8993(96)00174-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Slow IPSPs, which are believed to be involved in generation of the wave of spike-wave epileptiform discharges, are mediated by the GABA, receptor. We therefore examined the effect of the GABA, antagonist, Ciba Geigy Product, CGP-35348, in the cholesterol synthesis inhibitor model of absence epilepsy in rat. Rats received Ayerst-9944 (AY-9944), from 6-45 mg i.p. in the first few weeks of life. By 2 months after AY-9944 administration these rats exhibited recurrent spike-waves and behavioral arrests. In 10 such animals CGP-35348 was administered intraperitoneally in doses of 0 (vehicle), 10, 25 or 100 mg/kg. EEG recordings were obtained via previously implanted bone screws. Technologists blinded to treatment group counted spike-waves over a 4 h period post-injection. The average number of spike-wave burst seconds per 4 h of recording for all dosages and times was 52.4 +/- 81.4 (mean +/- S.D.) s. Mean burst times (seconds) were vehicle = 93.5 +/- 106.5; 10 mg/kg = 69.9 +/- 79.7; 25 mg/kg = 30.8 +/- 46.9; 100 mg/kg = 15.2 +/- 54, a mean 84% reduction at 100 mg/kg (ANOVA regression significant at 0.0001). Spike-waves were suppressed for at least 4 h after injection of CGP-35348. These findings supplement similar findings in other absence models, and support a potential role for GABA(B) antagonists in treatment of absence seizures.
引用
收藏
页码:147 / 150
页数:4
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