Bicuculline epileptogenesis in the rat

Bicuculline has been applied electrophoretically from a fluid filled microelectrode at different depths within the primary somatosensory area of the cerebral cortex of rats anaesthetized with urethane. The delay between onset of drug application at a constant rate and onset of spontaneous focal interictal epileptiform discharges (FIEDs), detected by a nearby recording microelectrode, was least when bicuculline was applied at a depth of 0.65 mm below the pial surface. The subsequent frequency of FIEDs and their voltage excursion were also greatest at this depth. The relationship between the delay of onset of epileptiform spiking and the depth of drug application was very similar to that previously determined for penicillin. This similarity of the sensitivity profiles suggests that the epileptogenic actions of the two agents may be attributable to a common mechanism. At low concentrations, both agents specifically block GABAergic inhibitory synaptic transmission in brain tissue. This is likely to be the mechanism of their epileptogenic effects. Other synaptic and non-synaptic mechanisms cannot, however, be ruled out because of the high concentrations which are achieved locally when a chemical is applied from a point source.