Wláz P, Potschka H, Löscher W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Epilepsy Res. 1998 May;30(3):219-29. doi: 10.1016/s0920-1211(98)00008-4.
Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may represent a more humane alternative to the widely used transcorneal stimulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced seizures. In addition, we stimulated mice and rats repeatedly via transcorneal 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 supramaximal stimulation (50 mA). Frontal stimulation resulted in lower convulsive threshold than in the case of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in seizure threshold for both 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. Supramaximal stimulation (50 mA) yielded comparable ED50 values regardless of the site of stimulation. Furthermore, once-daily stimulation of mice, regardless of the placement of electrodes, did not induce any changes in convulsive threshold. We also attempted to kindle mice and rats via corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kindling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindling. Moreover, corneal stimulation was better tolerated by rats, while in mice high mortality was seen after either method of current delivery. Our data indicate that frontal electrodes can be used as an alternative to transcorneal stimulation to produce MES by supramaximal or threshold current intensities as screening procedures in antiepileptic drug (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be useful to produce kindling in rats and mice.
额叶刺激，即通过将电极按压在小鼠或大鼠完整的额骨皮肤上进行电刺激，可能是一种比广泛使用的经角膜刺激诱导电休克惊厥更人道的替代方法。这项工作的目的是直接比较经角膜刺激和额叶刺激在诱发小鼠最大电休克惊厥（MES）方面的效果，以及卡马西平（CBZ）和苯妥英（PHT）对由此产生的惊厥的抗惊厥作用。此外，我们通过经角膜和额叶电极对小鼠和大鼠进行反复刺激，以观察这种方法是否会引发点燃效应。在小鼠中使用了两种电休克测试，即最大电休克惊厥阈值（MEST）测试和由超强刺激（50 mA）产生的MES。额叶刺激导致的惊厥阈值低于角膜刺激。CBZ和PHT对经角膜和额叶这两个刺激部位的惊厥阈值均产生剂量依赖性增加。就电极类型而言，与经角膜刺激相比，额叶刺激需要更高剂量的PHT来提高惊厥阈值。无论刺激部位如何，超强刺激（50 mA）产生的半数有效剂量（ED50）值相当。此外，无论电极放置位置如何，每天对小鼠进行一次刺激均未引起惊厥阈值的任何变化。我们还试图通过使用最初不会产生全身性阵挛性惊厥的电流进行重复电刺激，经角膜和额叶电极对小鼠和大鼠进行点燃。小鼠每天用3 mA（经角膜电极）或2 mA（额叶电极）刺激1次，每次2秒，大鼠每天用8 mA（经角膜电极）或5 mA（额叶电极）刺激2次，每次4秒。在大鼠中，经角膜刺激时点燃发展有明显进展，与经角膜刺激的小鼠相比，其性质不同。额叶刺激未产生点燃效应。此外，大鼠对经角膜刺激的耐受性更好，而在小鼠中，无论采用哪种电流传递方法，死亡率都很高。我们的数据表明，在抗癫痫药物（AED）开发的筛选过程中，额叶电极可作为经角膜刺激的替代方法，通过超强或阈值电流强度产生MES。然而，这种类型的刺激不能用于产生最小电休克惊厥，似乎也无助于在大鼠和小鼠中产生点燃效应。
