AMPHETAMINE INDUCES HYDROXYL RADICAL FORMATION IN THE STRIATUM OF RATS

Amphetamine-induced hydroxyl radical formation in the striatum of rats was investigated in this study. With the utilization of the microdial ysis and HPLC-ECD, the striatal dopamine (DA) release and the formatio n of 2,3-dihydroxybenzoic acid (2,3-DHBA), derived from the reaction o f hydroxyl radicals ( OH) and salicylate in perfusion, were monitored and detected during desipramine and/or amphetamine (AMPH) administrati on. Our data revealed that after desipramine treatment AMPH injections not only amplified striatal DA release and 2,3-DHBA formation, but al so intensified the stereotyped behaviors induced by AMPH. Furthermore, we discovered that alpha-methyl-para-tyrosine (alpha-MT) pretreatment prevented the onset of the above responses. In desipramine-treated ra ts, the tissue homogenization study demonstrated that a single dose of AMPH produced long-term depletion of striatal DA; this was not seen i n saline-treated rats. Moreover, striatal DA depletion could be lessen ed by pretreatment with mannitol, a OH scavenger. These results indica te that AMPH-induced striatal OH formation might be DA-related in desi pramine-treated rats, and suggest that OH formation might be correlate d with AMPH-induced neurodegeneration.