Flash‐Evoked Afterdischarge in Rat as a Model of the Absence Seizure: Dose‐Response Studies with Therapeutic Drugs

Abstract

The flash-evoked afterdischarge (FEAD) is a self-sustained burst of wave-and-spike complexes recorded from occipital cortex in the rat and other animals in response to a single light flash. Based on behavioral experiments and studies using single doses of antiepileptic drugs, FEAD was proposed as a model of the absence seizure. To test the validity of FEAD as an absence seizure model, the present experiments determined dose-response relationships for the suppression of FEAD by 6 antiepileptic drugs with established clinical profiles. Phenobarbital, ethosuximide and trimethadone suppressed FEAD in a dose-related manner and ethosuximide was .apprx. 3 times as potent as trimethadione. Mephenytoin produced a maximal reduction of FEAD of only 30-40%, which was not dose-related. Phenytoin or acetazolamide did not suppress FEAD. The results obtained with ethosuximide, trimethadione and phenytoin are qualitatively similar to their therapeutic effects in absence epilepsy. The FEAD model failed to predict the therapeutic efficacy of mephenytoin or acetazolamide. It is similar to the metrazol seizure model. Apparently, FEAD is a valid absence seizure model with a pharmacological predictive value that is at least as good as the metrazol model.