A glycine antagonist 7-chlorokynurenic acid attenuates ischemia-induced learning deficits.
Transient global ischemia can result in permanent neuronal damage and impairments in learning and memory. We investigated the therapeutic potential of 7-Chlorokynurenic acid, a potent antagonist at the glycine-modulatory site on the NMDA receptor, in terms of both neuroprotection and behavioral outcome in rats following transient forebrain ischemia. Intraventricular administration of the drug immediately before ischemia significantly attenuated ischemia-induced CA1 pyramidal cell loss. Moreover, ischemic rats treated with 7-Chlorokynurenic acid showed unimpaired acquisition of a delayed nonmatching to sample task 8 weeks following surgery, whereas saline-treated ischemic rats were significantly impaired. These data provide preliminary evidence that the glycine site may be an appropriate target for therapeutic agents in ischemia.
Wood
E R
ER
Department of Psychology, University of British Columbia, Vancouver, Canada.
Bussey
T J
TJ
Phillips
A G
AG
D000704:Analysis of Variance; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004192:Discrimination, Psychological / Q000187:drug effects; D005998:Glycine / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000523:psychology*; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D007859:Learning Disabilities / Q000517:prevention & control*; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine