SUPPRESSION OF CORTICAL EPILEPTIC AFTERDISCHARGES BY KETAMINE IS NOT STABLE DURING ONTOGENY IN RATS

Anticonvulsant action of ketamine, a noncompetitive NMDA antagonist, w as 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 pheno mena could be recorded. Stimulation (bipolar pulses of 1-ms duration a nd 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 d oses of 5, 10, 20, or 40 mg/kg. Control groups did not receive any dru g. Ketamine shortened ADs and suppressed motor correlates of stimulati on as well as of ADs in a dose-dependent manner in 12- and 25-day-old rats. No significant changes were observed in Ii-day-old animals, demo nstrating thus a rather complicated development of anticonvulsant acti on of ketamine. Not only NMDA antagonism, but also other possible effe cts of ketamine must be taken into account.