Involvement of excitatory amino acid mechanisms in gamma-hydroxybutyrate model of generalized absence seizures in rats.
gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures.
Banerjee
P K
PK
Childrens Hospital of Los Angeles, Department of Neurology, University of Southern California, School of Medicine 90027.
Snead
O C
OC
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012978:Sodium Oxybate; D013331:Strychnine / Q000494:pharmacology
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D012978:Sodium Oxybate; D013331:Strychnine