NMDA receptor antagonists inhibit kindling epileptogenesis and seizure expression in developing rats.
N-Methyl-D-aspartate (NMDA) receptor antagonists inhibit both the kindling process and the expression of seizures in previously kindled adult rats. Experimental seizures are more readily produced in infant than adult rats, possibly related to a developmental predominance of NMDA receptor-mediated effects. If so, reduction of seizure susceptibility by NMDA receptor antagonists should be more dramatic in infant rats than in adults. We studied the effect of ketamine and MK-801 on kindling epileptogenesis and seizure expression in 15-day-old rats. Ketamine (5, 10, and 20 mg/kg) and MK-801 (0.033 and 0.1 mg/kg) both significantly increased the latency to stage 3 or 4 seizures in dose-dependent fashion. These results were similar to those found in adults but occurred at slightly lower doses. Ketamine 20 mg/kg and MK-801 0.33 mg/kg totally eliminated clinical seizure activity and nearly abolished afterdischarge in previously kindled infant rats, effects exceeding those reported in adults using doses up to 6 times as great. These results support the hypotheses that NMDA receptor-mediated neurotransmission plays an important role in seizure production and the increased seizure susceptibility in immature brain and raise the possibility that NMDA receptor antagonists could be useful antiepilepsy agents in young children.
Trommer
B L
BL
Department of Pediatrics, Northwestern University Medical School, Evanston Hospital, IL 60201.
Pasternak
J F
JF
D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D007649:Ketamine / Q000494:pharmacology*; D007696:Kindling, Neurologic; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007649:Ketamine; D016291:Dizocilpine Maleate