The effect of the non-NMDA receptor antagonist GYKI 52466 and NBQX and the competitive NMDA receptor antagonist D-CPPene on the development of amygdala kindling and on amygdala-kindled seizures.
A competitive (NBQX) and a non-competitive (GYKI 52466) AMPA antagonist, and a competitive NMDA antagonist (D-CPPene) were tested against the development of kindling and against fully kindled seizures in amygdala-kindled rats. GYKI 52466, 10 mg/kg given i.p. 5 min prior to electrical stimulation in fully kindled animals, reduces both the cortical after-discharge duration and the behavioural seizure score. GYKI 52466, 20 mg/kg, reduces seizure score and after-discharge duration significantly (after 5-30 min) but the animals show severe motor side effects and an irregular cortical and hippocampal EEG. Administration of GYKI 52466, 10 mg/kg, prior to kindling stimulation on days 3-8, does not slow the development of kindling. NBQX, 20 mg/kg or 40 mg/kg i.p., 30 min prior to stimulation, significantly reduces the seizure score in fully kindled animals. NBQX 20 mg/kg i.p. has no effect on the development of kindling. D-CPPene, 8 mg/kg or 12 mg/kg, 120 min prior to stimulation reduces the behavioural seizure score in fully kindled animals. D-CPPene, 8 mg/kg on days 3-8, delays the development of kindling. NMDA receptors play a key role in the kindling process. Expression of kindled seizures involves non-NMDA and NMDA receptors.
Dürmüller
N
N
Department of Neurology, Institute of Psychiatry, Denmark Hill, London, UK.
Craggs
M
M
Meldrum
B S
BS
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014151:Anti-Anxiety Agents; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D004558:Electric Stimulation; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; C065286:SDZ EAA 494