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Abstract
Slow IPSPs, which are believed to be involved in generation of the wave of spike-wave
epileptiform discharges, are mediated by the GABAB receptor. We therefore examined
the effect of the GABAB 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 GABAB antagonists in treatment of absence seizures.