In vivo hydroxyl radical formation after quinolinic acid infusion into ratcorpus striatum

We studied the effect of an acute infusion of quinolinic acid (QUIN) on in vivo hydroxyl radical ((OH)-O-.) formation in the striatum of awake rats. U sing the microdialysis technique, the generation of OH was assessed through electrochemical detection of the salicylate hydroxylation product 2,3-dihy droxybenzoic acid (2,3-DHBA). The OH extracellular levels increased up to 3 0 times over basal levels after QUIN infusion (240 nmol/mul), returning to the baseline 2 h later. This response was attenuated, but not abolished, by pretreatment with the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.) 60 min before QUIN infusion. The mitochondrial toxin 3-nitroproplonic acid (3- NPA, 500nmol/mul) had stronger effects than QUIN on (OH)-O-. generation, as well as on other markers of oxidative stress explored as potential consequ ences of (OH)-O-. increased levels, These results support the hypothesis th at early OH generation contributes to the pattern of toxicity elicited by Q UIN. The partial protection by MK-801 suggests that QUIN neurotoxicity is n ot completely explained through NMDA receptor overactivation, but it may al so involve intrinsic QUIN oxidative properties. NeuroReport 12:2693-2696 (C ) 2001 Lippincott Williams & Wilkins.