Ontogeny of gamma-hydroxybutyric acid. II. Electroencephalographic effects

The ontogeny of petit mal-like seizures induced by gamma-hydroxybutyrate (GHB) was investigated. The prodrug of GHB, gamma-butyrolactone (GBL) was administered in varying dosages under continuous EEG monitoring from cortical and depth electrodes to rats varying in postnatal age from 1 to 85 days. The brain pharmacokinetics of GHB were determined at various ages as was the effect of ethosuximide on GBL-induced EEG changes. In adult rats, GBL produced a predictable sequence of electrical events beginning with spike bursts and progressing to polyspiking separated by low voltage activity. In 1-day-old rats, GBL produced voltage suppression with stupor. Poorly organized spiking appeared at postnatal day 3 and by day 9 marked burst suppression with polyspiking separated by low voltage activity was noted. However, the full array of electrical events seen in adult rats did not appear until day 28. Ethosuximide was ineffective against GHB seizure until the third postnatal week of life. GHB had a longer half-life in brain in the first week of postnatal life. These data suggest that in the rodent, petit mal-like seizure activity may require a fully mature brain and raise the possibility of different mechanisms being responsible for the various stages of EEG changes induced by GBL.