Flash-evoked afterdischarge in rat as a model of the absence seizure: dose-response studies with therapeutic drugs.
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. On the basis of behavioral experiments and studies employing single doses of antiepileptic drugs, FEAD has been proposed as a model of the absence seizure. In order to test the validity of FEAD as an absence seizure model, the present experiments determined dose-response relationships for the suppression of FEAD by six antiepileptic drugs with established clinical profiles. It was found that phenobarbital, ethosuximide, and trimethadione suppressed FEAD in a dose-related manner, and that ethosuximide was approximately three times as potent as trimethadione. Mephenytoin produced a maximal reduction of FEAD of only 30 to 40%, which was not dose-related. Neither phenytoin nor acetazolamide suppressed FEAD. The results obtained with ethosuximide, trimethadione, and phenytoin are qualitatively similar to their therapeutic effects in absence epilepsy. The FEAD model failed, however, to unequivocally predict the therapeutic efficacy of mephenytoin or acetazolamide. In this respect, it is similar to the metrazol seizure model. It is concluded that FEAD is a valid absence seizure model with a pharmacological predictive value that is at least as good as the metrazol model.
D000086:Acetazolamide / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005013:Ethosuximide / Q000627:therapeutic use; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D008617:Mephenytoin / Q000627:therapeutic use; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D010775:Photic Stimulation; D051381:Rats; D012640:Seizures / Q000188:drug therapy*; D014293:Trimethadione / Q000627:therapeutic use
D005013:Ethosuximide; D010672:Phenytoin; D000086:Acetazolamide; D008617:Mephenytoin; D014293:Trimethadione; D010634:Phenobarbital