Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine

The mechanism of 3,4-methylenedioxymethamphetamine (MDMA)-induced depletion of brain serotonin (5-hydroxytryptamine, 5-HT) has been proposed to involv e the generation of reactive oxygen species. In the present study, quantifi cation of the extracellular concentration of 2,3-dihydroxybenzoic acid (2,3 -DHBA) from salicylic acid was used as an index of hydroxyl radical generat ion. Although both MDMA and D-amphetamine markedly increased the extracellu lar concentration of dopamine in the striatum, only MDMA increased the extr acellular concentration of 2,3-DHBA. Treatment with fluoxetine either 1 h p rior to or 4 h following the administration of MDMA reduced the MDMA-induce d formation of 2,3-DHBA and also attenuated the MDMA-induced depletion of 5 -HT in the striatum. These results are supportive of the view that the MDMA -induced generation of hydroxyl radicals and. ultimately, the long-term dep letion of 5-HT, is dependent, in part. on the activation of the 5-HT transp orter. (C) 1999 Elsevier Science B.V. All rights reserved.