Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum.
The formation of hydroxyl radicals following the systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) was studied in the striatum of the rat by quantifying the stable adducts of salicylic acid and D-phenylalanine, namely, 2,3-dihydroxybenzoic acid (2,3-DHBA) and p-tyrosine, respectively. The repeated administration of MDMA produced a sustained increase in the extracellular concentration of 2,3-DHBA and p-tyrosine, as well as dopamine. The MDMA-induced increase in the extracellular concentration of both dopamine and 2,3-DHBA was suppressed in rats treated with mazindol, a dopamine uptake inhibitor. Mazindol also attenuated the long-term depletion of serotonin (5-HT) in the striatum produced by MDMA without altering the acute hyperthermic response to MDMA. These results are supportive of the view that MDMA produces a dopamine-dependent increase in the formation of hydroxyl radicals in the striatum that may contribute to the mechanism whereby MDMA produces a long-term depletion of brain 5-HT content.
Shankaran
M
M
College of Pharmacy, University of Cincinnati, Ohio 45267-0004, USA.
Yamamoto
B K
BK
Gudelsky
G A
GA
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000493:pharmacokinetics; D012701:Serotonin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D062385:Hydroxybenzoates; D012701:Serotonin; D017665:Hydroxyl Radical; D014443:Tyrosine; D010649:Phenylalanine; C009135:2,3-dihydroxybenzoic acid; D008454:Mazindol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D020156:Salicylic Acid