FRONTAL VERSUS TRANSCORNEAL STIMULATION TO INDUCE MAXIMAL ELECTROSHOCK SEIZURES OR KINDLING IN MICE AND RATS

Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may r epresent a more humane alternative to the widely used transcorneal sti mulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting max imal electroshock-induced seizures (MES) in mice and the anticonvulsan t effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced s eizures. In addition, we stimulated mice and rats repeatedly via trans corneal and frontal electrodes to see whether kindling is produced by this procedure. Two electroshock tests were used in mice, i.e. maximal electroshock seizure threshold (MEST) test and MES generated by supra maximal stimulation (50 mA). Frontal stimulation resulted in lower con vulsive threshold than in the case of corneal stimulation. Both CBZ an d Pi-IT produced dose-dependent increases in seizure threshold for bot h sites of stimulation, i.e. transcorneal and frontal. As regards type of electrodes, higher doses of PHT were required to increase seizure threshold in the case of frontal than transcorneal stimulation. Supram aximal stimulation (50 mA) yielded comparable ED,, values regardless o f the site of stimulation. Furthermore, once-daily stimulation of mice , regardless of the placement of electrodes, did not induce any change s in convulsive threshold. We also attempted to kindle mice and rats v ia corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic sei zures. Mice were stimulated once daily for 2 s with 3 mA (corneal elec trodes) or 2 mA (frontal electrodes) and rats were stimulated twice da ily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kin dling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindlin g. Moreover, corneal stimulation was better tolerated by rats, while i n mice high mortality was seen after either method of current delivery . Our data indicate that frontal electrodes can be used as an alternat ive to transcorneal stimulation to produce MES by supramaximal or thre shold current intensities as screening procedures in antiepileptic dru g (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be usef ul to produce kindling in rats and mice. (C) 1998 Elsevier Science B.V . All rights reserved.