Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis. II. The effects of MK-801.
MK-801 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant and neuroprotective properties. The action of MK-801 (0.05-10 mg/kg IP) was assessed against pentylenetetrazol-induced seizures (PTZ; 100 mg/kg SC; 30 min after MK-801) in rats aged 7, 12, 18, 25, and 90 days (N = 263). We observed pronounced ataxia and hypermobility after MK-801 pretreatment during the whole ontogenesis, and the animals exhibited head-weaving and body-rolls. After the combination of MK-801 and PTZ "wet dog shakes" were detected in 18-, 25-, and 90-day-old rats (never seen in controls receiving PTZ only). MK-801 only insignificantly modified the latencies of minimal (clonic) seizures in 18-day-old and older rats where this seizure type is regularly elicited. In 12-day-old rats an increased incidence of minimal seizures was detected. MK-801 nearly completely blocked or strongly delayed major (generalized tonic-clonic) seizures and attenuated the seizure severity during ontogenesis in a dose-dependent manner. Present results suggest the important role of NMDA receptors in the genesis of generalized tonic-clonic seizures whilst the role of NMDA receptors in minimal seizures appears to be negligible during the whole ontogenetic development.
Velísek
L
L
Institute of Physiology, Czechoslovak Academy of Sciences, Prague.
Veresová
S
S
Pôbisová
H
H
Mares
P
P
D000375:Aging / Q000502:physiology; D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004831:Epilepsies, Myoclonic / Q000139:chemically induced; D008297:Male; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced*
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D010433:Pentylenetetrazole