Characterization of hydroxyl radical generation in the striatum of free-moving rats due to carbon monoxide poisoning, as determined by in vivo microdialysis

Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min resulted in stimulation of hydroxyl radical (circleOH) generation (estimated by measuring 2,3-dihydroxybenzoic acid (2,3-DHBA) production from salicylic acid) in the striatum of free-moving rats, as determined by means of brain microdialysis. Pretreatment with a voltage-dependent Na+ channel blocker, tetrodotoxin (TTX), lowered the basal level of 2,3-DHBA and strongly suppressed the increase in 2,3-DHBA induced by CO poisoning. CO poisoning significantly, though only slightly, increased extracellular glutamate in the striatum, and glutamate (Glu) receptor antagonists, such as MK-801 (dizocilpine) and NBQX,. failed to suppress the CO-induced increase in 2,3-DHBA. These findings suggest that CO poisoning may induce Na+ influx via the voltage-dependent Na+ channels, resulting in stimulation of circleOH generation in rat striatum. This effect may be independent of Glu receptor activation by increased extracellular Glu. (C) 2004 Elsevier B.V. All rights reserved.