Pre- and post-exposure talampanel (GYKI 53773) against kainic acid seizures in neonatal rats

BackgroundAMPA receptors play an important role in the neurobiology of neonatal epilepsy. The present study evaluated the effect of talampanel, a potent and selective non-competitive antagonist of AMPA receptors, against kainic acid-induced continuous seizures (status epilepticus) and other behavioral abnormalities in neonatal rats.MethodsKainic acid was administered at doses of 2 or 4 mg/kg, ip to induce seizures and status epilepticus in postnatal 7 days old rat neonates in pre- and post-exposure studies, respectively.ResultsIntraperitoneal administration of kainic acid (2 or 4 mg/kg) resulted in forelimb/hind-limb scratching defined as automatism, continuous generalized tonic–clonic seizures with loss of righting reflex suggesting status epilepticus and tonic extension. Pre-exposure of talampanel (2.5–10 mg/kg, ip) 30 min before kainic acid did not affect the onset of kainic acid convulsions. Talampanel at 20 mg/kg, ip delayed the commencement of tonic extension, but not status-induced by kainic acid. In contrast, talampanel (5 and 10 mg/kg, ip) when administered 5 min after kainic acid (4 mg/kg, ip) postponed the onset of status epilepticus and tonic extension compared to vehicle treated group. Furthermore, talampanel (10 mg/kg, ip) but not GYKI 52466 (20 or 50 mg/kg, ip; a non-competitive AMPA/kainate receptor antagonist) stopped the ongoing status epilepticus when administered 10 min after the administration of kainic acid. However, seizures re-occurred after 35.98 ± 2.36 min.ConclusionThe present results suggested that talampanel is protective in kainic acid-induced neonatal status epilepticus model; however, the time of administration is a crucial factor in determining its effectiveness.