Picrotoxin-induced tonic-clonic seizures and lethality are decreased by MK-801 in developing rats.

The action of MK-801 (NMDA antagonist; 0.1 and 0.5 mg/kg, IP) was tested against picrotoxin-induced seizures (3-6 mg/kg, IP) in rats aged 7, 12, 18, 25, and 90 days. We found MK-801 only inconsistently affected clonic seizures in 12- and 25-day-old rats, whereas tonic-clonic seizures were suppressed or delayed in almost all age groups. In addition, the lethality of picrotoxin was diminished by the higher dose of MK-801 in all age groups. The results suggest: a) different generators for both seizure patterns (clonic and tonic-clonic), b) an involvement of NMDA receptors in the genesis of tonic-clonic seizure pattern, and c) an interaction of MK-801 with GABAergic transmission throughout the entire development studied.