Epileptic afterdischarges elicited by stimulation of sensorimotor cortex were chosen to test anticonvulsant effects of NMDA receptor antagonists in developing rats (12, 18 and 25 days old) with implanted electrodes. Afterdischarges were elicited four times with 10-min intervals in the experiments with dizocilpine and 20 min with the other two drugs.
Dizocilpine (0.5 or 1 mg/kg), CGP 40116 (0.1, 0.5 or 1 mg/kg) or 2-amino-7-phosphonoheptanoic acid (AP7, 30 or 60 mg/kg) was injected intraperitoneally between the first and second stimulation. Intensity of movements accompanying stimulation was diminished regularly only by CGP 40116.
Duration of afterdischarges was reduced and intensity of clonic seizures was decreased by CGP 40116 in all age groups; dizocilpine exhibited similar action in 25- and 18-day-old rats, AP7 only in 25-day-old animals. Anticonvulsant action of the three NMDA antagonists exhibited different developmental profiles in our model; this difference might be due to developmental changes of NMDA receptors.