The selective ionotropic-type quisqualate receptor agonist AMPA is a potent neurotoxin in immature rat brain.
Direct unilateral intrastriatal stereotaxic injections of the selective ionotropic-type quisqualate receptor agonist, AMPA, in postnatal day 7 rats produced tonic-clonic seizure activity. Quantitative analysis of the severity of brain injury was assessed by comparison of the disparities in the weights of injected and contralateral cerebral hemispheres 3 days after the excitotoxin injection. The amount of AMPA that produced half-maximal brain injury was 9.5 nmol as assessed by comparison of disparities in cerebral hemisphere weights. In contrast, quisqualate was 26 times less potent. The marked susceptibility of the developing rat brain to AMPA toxicity may provide a useful model to assess the neuroprotective effectiveness and selectivity of ionotropic quisqualate receptor antagonists.
McDonald
J W
JW
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Trescher
W H
WH
Johnston
M V
MV
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D007267:Injections; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid