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 microdialysis and HPLC-ECD, the striatal dopamine (DA) release and the formation of 2,3-dihydroxybenzoic acid (2,3-DHBA), derived from the reaction of hydroxyl radicals (.OH) and salicylate in perfusion, were monitored and detected during desipramine and/or amphetamine (AMPH) administration. Our data revealed that after desipramine treatment AMPH injections not only amplified striatal DA release and 2,3-DHBA formation, but also 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 rats, the tissue homogenization study demonstrated that a single dose of AMPH produced long-term depletion of striatal DA; this was not seen in saline-treated rats. Moreover, striatal DA depletion could be lessened by pretreatment with mannitol, a .OH scavenger. These results indicate that AMPH-induced striatal .OH formation might be DA-related in desipramine-treated rats, and suggest that .OH formation might be correlated with AMPH-induced neurodegeneration.
Huang
N K
NK
Graduate Institute of Life Sciences, Taiwan, Republic of China.
Wan
F J
FJ
Tseng
C J
CJ
Tung
C S
CS
D000661:Amphetamine / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D008845:Microinjections; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; D009287:Naphthyridines; D012459:Salicylates; D017665:Hydroxyl Radical; D009268:Nalidixic Acid; D019805:alpha-Methyltyrosine; C009135:2,3-dihydroxybenzoic acid; D000661:Amphetamine; C006486:amfonelic acid; D004298:Dopamine