Noradrenergic mechanisms in gamma-hydroxybutyrate-induced seizure activity

The electroencephalographic (EEG) response of 6-hydroxydopamine (6-OHDA)-treated and control rats to gamma-butyrolactone (GBL) the prodrug of gamma-hydroxybutyrate (GHB), was determined. Neonatal treatment with 6-OHDA produced a significant reduction of noradrenaline in cortex and hippocampus while sparing noradrenaline in the hypothalamus. Brain dopamine was unaffected. The electrographic seizure produced by GBL was significantly prolonged and more severe in the 6-OHDA-treated animals. That portion of the hypersynchronous seizure induced by GBL which is pharmacologically sensitive to antipetit mal anticonvulsants, Stage 1, was however shortened in the 6-OHDA-treated animals. Reduction of forebrain noradrenaline seems to have a complex effect on GBL-induced seizure in that it results in a reduction of hypersynchronous EEG activity but in a prolongation of the more severe EEG changes of burst suppression normally seen with higher doses of GBL.