INCREASE IN HYDROGEN-PEROXIDE CONCENTRATION IN THE RAT STRIATUM AFTER HALOPERIDOL ADMINISTRATION

Acute administration of neuroleptics cause an acceleration in the turn over of dopamine metabolism in brain. On the process of dopamine metabolism, hydrogen peroxide is generated through an action of monoamine oxidase. Then, hydrogen peroxide appears to be converted to hydroxyl radical, one of the most toxic active oxygen species. Thus, neuroleptics may act as neurotoxin via action of active oxygen species. As a first step for the examination of the hypothesis, rats received intraperitoneal administration of 1.5 and 4.5 mg/kg of haloperidol, and hydrogen peroxide concentration was measured in the striatum, by using hydrogen peroxide sensor. After 1.5 mg/kg of haloperidol, there was no alteration in concentration of hydrogen peroxide. However, 4.5 mg/kg of haloperidol caused a significant elevation of hydrogen peroxide concentration from 4 to 32 min after injection. These findings suggest that in the rat striatum, haloperidol stimulates a generation of active oxygens, which may participate in the pathogenesis of tardive dyskinesia.