[Intracerebral-ventricular injection of 4-aminopyridine induced convulsion in rabbits]

Intracerebral-ventricular (icv) injection of 4-aminopyridine (4-AP) 8 micrograms to rabbits generated convulsions and epileptic discharges in electrocorticogram (ECoG). With 40 rabbits, the occurrence of convulsion at this dose level was 100%. The results from five rabbits showed that seizures may break out repeatedly at intervals of 1-5 min and such state may last about 1.5 h. Antiepileptic drugs, such as phenytoin sodium, phenobarbital sodium and diazepam, were found to effectively control the seizures provoked by icv 4-AP. Sodium valproate was less effective than the foregoing drugs. The icv 4-AP-induced convulsion appeared to have some merits as compared with the old epilepsy models, such as those induced by electric stimulation, cardiazol, or icv ferrous sulfate. We feel that it may be recommended as a model for the preliminary screening of antiepileptic drugs. The seizures provoked by icv 4-AP were shown to be antagonized by scopolamine, haloperidol, phentolamine, or propranolol, but potentiated by l-dopa. It is now recognized that 4-AP can enhance the release of ACh, DA, and NE in the central nervous system. The present results suggest that the convulsion elicited by 4-AP seems to be related to the disturbance of synaptic transmission in the brain.