Effects of repeated systemic penicillin injections on nonconvulsive and convulsive epileptic seizures in the rat.

Changes in the spontaneous and induced epileptic activity in the course of repetitive systemic i.p. administration of crystalline penicillin (Pc) were examined in imp-DAK rats. In all the rats used, nonconvulsive seizures characterized by bursts of spike and wave discharges (SWD) in the neocortex occurred spontaneously. A single i.p. injection of Pc at doses of 1,000,000, 1,500,000 or 2,000,000 IU/kg resulted in a transient increase in SWD activity. For the latter two doses, Pc injections also induced convulsive activity, i.e. single spikes and trains of spikes accompanied by myoclonies. When 1,500,000 IU/kg of Pc was administered repeatedly (six injections, one every 48 h), the amount of the convulsive activity induced by successive injections decreased but the increase in the number of SWD bursts became more pronounced. This result gives rise to some questions about the development of tolerance to the epileptogenic Pc effects in the course of repeated administration of this antibiotic.