Effects of the GABA-uptake inhibitor tiagabine on electroencephalogram, spike-wave discharges and behaviour of rats

Abstract

Effects of the anticonvulsant tiagabine in doses of 1, 3 and 10 mg/kg were investigated on electroencephalogram (EEG), spike-wave discharges and behaviour of WAG/Rij rats. These rats are considered as an animal model of generalized, non-convulsive, absence epilepsy. WAG/Rij rats spontaneously show a considerable number of spike-wave discharges in their EEG. These discharges can be facilitated by GABA agonists. The facilitatory effects of these agonists are completely opposite to their effects on convulsive seizures, which are reduced by these drugs. Tiagabine enhances the effects on the GABA system, since it acts as a GABA re-uptake inhibitor. According to expectations, tiagabine enhanced in a dose-related way both the number and mean duration of spike-wave discharges. The low dose of 1 mg/kg had almost no effects, but doses of 3 and 10 mg/kg were effective. Furthermore, tiagabine in the latter two doses increased the power in the higher beta band of the background EEG, whereas no significant changes in behavioural parameters were found. An unexpected finding was the occurrence of a second type of spike-wave discharges. These were again seen with the two higher doses of tiagabine, while 1 mg/kg had no effect. An assumption is that this second type of discharges are forerunners of genuine spike-wave discharges. In general, this experiment supports that non-convulsive epilepsy is associated with a GABA hyperfunction. It also underlines the biochemical differences of convulsive and non-convulsive animal models of epilepsy. Tiagabine, with its GABA-mimetic properties, belongs to the category of drugs effective in convulsive animal models and not in non-convulsive models of epilepsy.