GABA uptake blocker NNC-711 exhibits marked anticonvulsant action in two cortical epileptic models in immature rats

Purpose: To study the anticonvulsant action of a gamma-aminobutyric acid (G ABA) uptake inhibitor NNC-711 in two models of cortical epileptogenesis in immature rats. Methods: Twelve-, 18-, and 25-day-old rat pups with implanted electrodes we re used in this study. Epileptogenic foci were elicited by a local applicat ion of bicuculline methiodide (BMI) on the sensorimotor cortical region by means of an implanted cannula, and cortical epileptic afterdischarges (ADs) were induced by low-frequency stimulation (8 Hz) of the same cortical area . Epileptogenic foci were formed after pretreatment with NNC-711 (1 or 10 m g/kg, i.p.), and epileptic ADs were elicited in the second experimental ser ies. Then NNC-711 was administered in the same doses, and stimulation was r epeated. Results: NNC-711 did not block the formation of epileptogenic foci, but it significantly suppressed the spontaneous transition of interictal focal int o ictal activity in all age groups. The intensity of movements accompanying stimulation of the sensorimotor cortex was less under the influence of NNC -711 in the 18- and 25-day-old rats, The duration of cortical ADs was short ened in all age groups, but transient abolition of ADs was observed only af ter the higher dose in the 25-day-old rats. In addition, the intensity of c lonic seizures appearing during ADs decreased, and the transition of ADs in to another type due to an involvement of limbic structures failed to appear in the 18- and 25-day-old rats. Conclusions: Primary epileptogenesis in the cerebral cortex was hardly infl uenced by NNC-711, but the spread of epileptic activity was markedly suppre ssed. This effect was better expressed in the 18- and 25-day-old animals th an in the youngest group.