Bicuculline methiodide in the blood-brain barrier-epileptogen model of epilepsy

Focal epilepsy can be produced by a blood-brain barrier (BBB)-excluded systemic convulsant (penicillin, folic acid, etc.) in the presence of a focal BBB lesion. Bicuculline methiodide, a gamma-aminobutyric acid blocking epileptogen, crosses the normal BBB of rats poorly and produces no consistent abnormality behaviorally or on EEG at 36 mg/kg. When the BBB is opened in 0.25 ml of cortex by 6,000 rad of alpha particles, by a pin trauma lesion, or by a heat lesion, the rats are normal clinically and on EEG. When these lesioned rats are challenged with bicuculline methiodide, 36 mg/kg, an intense, highly localized epileptiform discharge results that begins approximately 20 min after injection and lasts 30-90 min. The plausibility and experimental utility of the BBB-epileptogen model of epilepsy are enhanced by these observations.