Dizocilpine, ketamine and ethanol reverse NMDA-induced EEG changes and convulsions in rats and mice.
Electroencephalographic (EEG) activity in neocortex of rats following intracerebroventricular (icv) administration of NMDA (0.25-2 nmol/10 microliters) and its modification by noncompetitive NMDA-receptor antagonists, dizocilpine (MK-801) (0.025-0.1 mg/kg, ip) and ketamine (10-50 mg/kg, ip) was recorded at 0, 0.5, 4, 8 and 24 hr with chronically implanted electrodes. NMDA (0.25 and 1 nmol) showed longer lasting decrease in frequency in cortical neurons while 2 nmol produced convulsions and death. Administration of MK 801 (0.05 mg/kg) and ketamine (50 mg/kg) prior to NMDA offered protection in 40% of animals against NMDA-induced convulsions and blocked NMDA-induced long term influence. However, ketamine and MK 801 showed an increase in percent amplitude and also had long lasting effects per se. In conscious mice, NMDA (0.5-10 nmol/microliters icv) induced dose dependent convulsions. Both MK 801 and ketamine showed potent anticonvulsant effect. Ethanol (0.5-2 g/kg, ip) also offered significant protection against NMDA-induced convulsions. MK 801 (0.1 mg/kg) when administered concurrently with ethanol (0.5 g/kg) exhibited synergistic anticonvulsant effect. The EEG study in rats and effect of NMDA in conscious mice provide a direct evidence for the role of NMDA-receptor system in convulsions and in anticonvulsant action of ethanol.
Sharma
A C
AC
Department of Pharmaceutical Sciences, Panjab University, Chandigarh.
Thorat
S N
SN
Nayar
U
U
Kulkarni
S K
SK
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate