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.
Institute of Physiology, Czechoslovak Academy of Sciences, Prague, Czech Republic.
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Kubová
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D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000254:growth & development* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D009068:Movement / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D007649:Ketamine