Parenteral penicillin epilepsy: tolerance to subsequent treatments

We recorded spike activity induced by i.p. penicillin injections in eight rats, repeating the experiment five times per each rat, at 48-h intervals. Spike frequency was significantly reduced in all sessions subsequent to the first, without changes in penicillin blood concentrations. The penicillin model of epilepsy is therefore not advisable in studies on antiepileptic drugs with a crossover design.