ESTIMATING HYDROXYL RADICAL CONTENT IN RAT-BRAIN USING SYSTEMIC AND INTRAVENTRICULAR SALICYLATE - IMPACT OF METHAMPHETAMINE

Free radicals have been implicated in the etiology of many neurodegene rative conditions. Yet, because these species are highly reactive and thus short-lived it has been difficult to test these hypotheses. We ad apted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quantifiable products, 2,3-dihydrox ybenzoic acid (DHBA) and 2,5-DHBA. After systemic (100 mg/kg i.p.) or intraventricular (4 mu mol) administration of salicylate, the amount o f DHBA in striatal tissue correlated with tissue levels of salicylate. After systemic salicylate, the ratio of total DHBA to salicylate in n eostriatum was at least 10-fold higher than that observed after centra l salicylate. In addition, systemic salicylate resulted in considerabl y higher concentrations of 2,3- and 2,5-DHBA in plasma than in brain. Therefore, a large portion of the DHBA present in brain after systemic salicylate may have been formed in the periphery. A neurotoxic regime n of methamphetamine increased the concentration of DHBA in neostriatu m after either central or systemic administration of salicylate. The i ncrease in 2,3-DHBA after the central administration of salicylate was significant at 2 h, but not at 4 h, after the last dose of methamphet amine. These results suggest that (I)when assessing specific events in brain, it is preferable to administer salicylate centrally, and (2) n eurotoxic doses of methamphetamine increase the hydroxyl radical conte nt in brain in a time-dependent manner.