Effect of lazaroid pretreatment on dopamine-induced impairment of the rat nigrostriatal system.

Oxidative stress induced by enhanced catecholamine metabolism may subsequently cause damages to the nervous system. We used in vivo-pulse voltammetry to study an enhanced brain dopamine (metabolism) induced either by intranigral dopamine (DA) injection or reduction of cerebral blood flow. One week after intranigral injection of 10 microg DA or unilateral occlusion of one carotid the DA activity in the ipsilateral striatum was decreased as compared to the contralateral side. Three weeks after DA application and carotid clamping the DA activity was restored to normal. The significant reduction of 3,4-dihydroxyphenylacetic acid (DOPAC) after one week was attenuated by pretreatment with the lazaroid U-74389G, injected 20 min before surgery. The results are in accordance with the view that radical mechanisms play a crucial role in the impairment of the nigrostriatal system induced by oligemia.