Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum

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

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2516-2522
Number of pages7
JournalJournal of Neurochemistry
Volume72
Issue number6
DOIs
StatePublished - Jun 3 1999
Externally publishedYes

Keywords

  • 3,4-Methylenedioxymethamphetamine
  • Dopamine
  • Hydroxyl radical
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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