Increasing-current electroshock seizure test: a new method for assessment of anti- and pro-convulsant activities of drugs in mice.

We developed the increasing-current electroshock seizure (ICES) test, a new method for assessment of anti- and pro-convulsant activities of drugs in mice. In this method, a single train of pulses (square wave, 5 msec, 20 Hz) of linearly increasing intensity from 5 to 30 mA (increment of 0.1 mA/0.1 sec, i.e., 5-30 mA in 25 sec) was applied via ear electrodes. The current at which tonic hindlimb extension occurred was recorded as the seizure threshold. Thus, this method allows determination of the seizure threshold current for individual animals. Carbamazepine, phenytoin, valproate, phenobarbital, diazepam, and morphine all increased the seizure threshold current in a dose-dependent manner, whereas ethosuximide was not effective. The seizure threshold current decreased after treatment with reserpine, chlorpromazine, aminophylline, strychnine, pentylenetetrazol, bicuculline, picrotoxin, and ethyl-beta-carboline-3-carboxylate (beta-CCE). These results indicate that the ICES test, like the maximal electroshock seizure test, is a model of grand mal-type seizure and is useful for evaluation of both the anti- and pro-convulsant activities of drugs.