Ontogeny of ethosuximide action against two seizure models in rats is different

Action of ethosuximide (ESI) against two types of experimental seizures elicited by systemic administration of pentylenetetrazol (PTZ) and characterized by spike-and-wave activity in the EEG was studied in immature rats 18 and 25 days old, i.e. in such age groups where these age-dependent seizures could be reliably induced. Pretreatment with ESI in doses of 62.5 and 125 mg/kg i.p. suppressed episodes of spike-and-wave rhythm (rhythmic metrazol activity) elicited by a 40-mg/kg dose of PTZ in both age groups in a dose-dependent manner. Minimal metrazol seizures induced by higher dose of PTZ (70 mg/kg i.p.) were similarly suppressed by ESI in 25-day-old rats only. In 18-day-old animals ESI did not exhibit an anticonvulsant effect. These results speak against the adequacy of minimal metrazol seizures as a model of human absences. In addition, different development of ESI action against two types of experimental seizures suggests a possibility that there is more than one mechanism of action of ESI.