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

Mahalakshmi Shankaran, Bryan K. Yamamoto, Gary A. Gudelsky

Research output: Contribution to journalArticle

91 Scopus citations


The mechanism of 3,4-methylenedioxymethamphetamine (MDMA)-induced depletion of brain serotonin (5-hydroxytryptamine, 5-HT) has been proposed to involve the generation of reactive oxygen species. In the present study, quantification of the extracellular concentration of 2,3-dihydroxybenzoic acid (2,3-DHBA) from salicylic acid was used as an index of hydroxyl radical generation. Although both MDMA and D-amphetamine markedly increased the extracellular concentration of dopamine in the striatum, only MDMA increased the extracellular concentration of 2,3-DHBA. Treatment with fluoxetine either 1 h prior to or 4 h following the administration of MDMA reduced the MDMA-induced 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 depletion of 5-HT, is dependent, in part, on the activation of the 5-HT transporter. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Dec 3 1999
Externally publishedYes


  • 5-HT (5-hydroxytryptamine, serotonin)
  • Hydroxyl radical
  • MDMA (3,4-methylenedioxymethamphetamine)
  • Neurotoxicity

ASJC Scopus subject areas

  • Pharmacology

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