Kynurenic acid antagonizes hippocampal quinolinic acid neurotoxicity: behavioral and histological evaluation.
In the present study, we evaluate the ability of kynurenic acid to protect hippocampal neurons from the neurotoxicity of the N-methyl-D-aspartate (NMDA) agonist quinolinic acid. Bilateral intrahippocampal injection of quinolinic acid (120 nmol) led to severe behavioral disturbances and total loss of hippocampal neurons. Intrahippocampal co-injection of kynurenic acid (360 nmol) completely prevented cell loss and behavioral disturbances. However, the protection was incomplete when kynurenic acid was intraperitoneally injected (500 mg/kg, repeated during 4 days). These above results indicate that kynurenic acid can antagonize the neuronal degeneration mediated by excessive stimulation of NMDA receptors in vivo.
Lekieffre
D
D
Laboratoire de Pharmacologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Plotkine
M
M
Allix
M
M
Boulu
R G
RG
D000818:Animals; D005106:Exploratory Behavior / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D011805:Quinolinic Acids; D017378:Quinolinic Acid; D007736:Kynurenic Acid