FREE-RADICAL PRODUCTION DURING ETHANOL INTOXICATION, DEPENDENCE, AND WITHDRAWAL

Indices of free radical production and cell damage were examined in ma le Sprague-Dawley rats chronically exposed to either ethanol (ETOH) or water vapor. In experiment 1, rats experienced either 1 or 11 cycles of ETOH exposure and withdrawal. Brain tissue was harvested 12 hr afte r ETOH exposure, and 1 hr after being injected with sodium salicylate as a scavenger. Brain tissue was analyzed for the formation of salicyl ate hydroxylation products as a measure of . OH production during with drawal. Significant group differences for . OH production were demonst rated for 2,3- and 2,5-dihydroxybenzoic acid in the single cycle ETOH exposed rats compared with their water cohorts. A significant between group difference for 2,5-dihydroxybenzoic acid, only, was demonstrated for the multiple cycles of ETOH exposure, Spontaneous seizures were s hown to correlate with increased production of . OH in ETOH exposed ra ts. In experiment 2, brain tissue was harvested from different groups of rats after removal from the chambers, at 0, 2, 12, 24, 36, and 48 h r after a single exposure cycle, Tissue was analyzed for (1) salicylat e hydroxylation (as above), (2) glutamine synthetase activity, (3) who le brain glutamate concentration, and (4) oxidized protein. A multiple regression analysis was conducted on the five dependent variables and found they could be predicted by specific behavioral and neurological ratings, These data suggest that cell damage during withdrawal may ha ve multiple time-dependent components.