Objectives: We studied the electroencephalographic (EEG) and behavioral changes of the chemical model of generalized absence epilepsy induced by acute and chronic administration of gamma-butrolactone (GBL), a prodrug of gamma-hydroxybutyric acid.Methods: Adult male Wistar rats under anesthesia were implanted with bilateral cortical recording electrodes. The rats were administered 30 intraperitoneal injections of GBL twice daily from Monday to Friday and EEG was recorded 20 min before and 40 min after GBL injections. In order to monitor spontaneous spike-and-wave discharges (SWDs), the baseline EEGs on the subsequent Monday mornings after the first, second and third weekends were recorded for 90 min.Results: The intraperitoneal administration of GBL caused a rapid onset of bilaterally synchronous SWDs in the cortical EEG accompanied by behavioral immobility, vacant-staring and vibrissal twitching. By repeated GBL injections, animals displayed spontaneous bilateral synchronous SWDs in the baseline EEG on the Monday morning session after the GBL-free weekend period (60 h after the Friday afternoon injection).Conclusion: The present study reports the acute and chronic effects of the systemic administration of GBL. The chronic systemic application of GBL may represent a model of epileptogenesis for absence epilepsy.