Suppression of cortical epileptic afterdischarges by ketamine is not stable during ontogenesis in rats

Anticonvulsant action of ketamine, a noncompetitive NMDA antagonist, was studied in three groups of immature rats (12-, 18-, and 25-day-old) using cortically elicited epileptic afterdischarges (ADs) as a model. Rats with implanted electrodes were used, so that EEG and motor phenomena could be recorded. Stimulation (bipolar pulses of 1-ms duration and 8-Hz frequency) lasting 15 s was repeated four times with intervals of 10 min. Ketamine was administered IP 5 min after the first AD in doses of 5, 10, 20, or 40 mg/kg. Control groups did not receive any drug. Ketamine shortened ADs and suppressed motor correlates of stimulation as well as of ADs in a dose-dependent manner in 12- and 25-day-old rats. No significant changes were observed in 18-day-old animals, demonstrating thus a rather complicated development of anticonvulsant action of ketamine. Not only NMDA antagonism, but also other possible effects of ketamine must be taken into account.