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 th e rat by quantifying the stable adducts of salicylic acid and D-phenylalani ne, namely, 2,3-dihydroxybenzoic acid (2,3-DHBA) and p-tyrosine, respective ly. The repeated administration of MDMA produced a sustained increase in th e extracellular concentration of 2,3-DHBA and p-tyrosine, as well as dopami ne. The MDMA-induced increase in the extracellular concentration of both do pamine and 2,3-DHBA was suppressed in rats treated with mazindol, a dopamin e uptake inhibitor. Mazindol also attenuated the long-term depletion of ser otonin (5-HT) in the striatum produced by MDMA without altering the acute h yperthermic response to MDMA. These results are supportive of the view that MDMA produces a dopamine-dependent increase in the formation of hydroxyl r adicals in the striatum that may contribute to the mechanism whereby MDMA p roduces a long-term depletion of brain 5-HT content.