Abstract
The mechanism of action of the new anticonvulsant drug tiagabine (TGB) is reuptake inhibition of GABA. What TGB will do against nonconvulsive epilepsy is unclear. GABA agonists such as muscimol and anticonvulsants such as carbamazepine and phenytoin generally increase the number of spike-wave discharges (SWD). We wished to verify whether TGB would also facilitate the number of SWD in a genetic rat model for generalized absence epilepsy. Male WAGlRij rats with chronically implanted EEG electrodes were given either 0, 1, 3, or 10 mg/kg TGB intraperitoneally. The EEG was recorded for 1 h before and 2 h after drug administration. Behavior was recorded for 30 min postdrug; ambulation, passive behavior, and automatic behavior were scored.
TGB dose-dependently increased both the number and duration of SWD. The effect on the number lasted 75 min; the effect on SWD duration lasted slightly longer, -1.5 h. TGB had no effects on behavior, and the effects on the background EEG were slight: Only the 25.3-39.0-Hz band was enhanced. The most striking finding was the occurrence of type 2 SWD (Neurosci Lett 1986;70:393-7), an occipital EEG transient. These brief (<2 s) SWD occurred only after administration of the two highest TGB doses. The mean number was 104 after 10 mg/kg TGB. GABAergic drugs have opposite effects in convulsive and nonconvulsive epilepsy. The appearance of the brief type-2 SWD is unique for TGB. They deserve some attention, considering their large number and the fact that all rats at the highest dose showed these phenomena.
