Possible mediation of quinolinic acid-induced hippocampal damage by reactive oxygen species

Several differences exist between quinolinic acid and N-methyl-D-aspartate (NMDA) in the potency and pharmacology of their neurotoxic actions in the b rain, suggesting that quinolinic acid may act by mechanisms additional to t he activation of NMDA receptors, possibly involving lipid peroxidation. In the present review,studies are considered which have attempted to determine whether free radicals might contribute to the neuronal damage induced by q uinolinic acid. Following Injections into the hippocampus of anaesthetised rats, quinolinic acid induced damage is prevented by melatonin, by an actio n not blocked by the melatonin receptor blocker luzindole. Deprenyl, but no t the non-selective monoamine oxidase inhibitor nialamide, also prevent qui nolinic acid-induced damage. In vitro, seversl groups have shown that quino linic acid can induce lipid peroxidation of brain tissue The results sugges t that free radical formation contributes significantly to quinolinic acid- induced damage in vivo.