Epileptiform discharges induced by combined application of bicuculline and4-aminopyridine are resistant to standard anticonvulsants in slices of rats

Application of 4-aminopyridine (4AP) has previously been reported to produc e different patterns of epileptiform discharges in entorhinal cortex-hippoc ampal-slices. Here we describe that 4-AP induced epileptiform activity in t he EC becomes insensitive to anticonvulsant drugs (phenytoin, carbamazepine , valproic acid, phenobarbital) when GABAergic transmission is blocked by b icuculline. We propose that the activities induced by 4-aminopyridine and b icuculline may provide an in vitro model for the development of new drugs a gainst difficult-to-treat focal epilepsy. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.