Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists

Gary A. Gudelsky, Bryan K. Yamamoto, J. Frank Nash

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The effects of the 5-HT2 receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on 3,4-methylenedioxymethamphetamine (MDMA)-induced dopamine release and 5-HT depletion in the striatum were studied. The MDMA-induced increase in the extracellular concentration of dopamine in the striatum was enhanced significantly in rats treated with either DOI (2 mg/kg, ip.) or 5-MeODMt (15 mg/kg, ip.), as assessed using in vivo microdialysis. Neither DOI nor 5-MeODMT alone altered the extracellular concentration of dopamine in the striatum. The striatal concentration of 5-HT was decreased, but not significantly, 7 days following a single administration of MDMA (10 mg/kg, sc.). However, 7 days following the concomitant treatment with DOI and MDMA the striatal concentration of 5-HT was significantly less than that in rats treated with MDMA alone or the vehicle-treated controls. It is concluded that activation of 5-HT2 receptors is an important determinant of the acute increase in extracellular dopamine and, consequently, the long-term depletion of brain 5-HT produced by MDMA.

Original languageEnglish (US)
Pages (from-to)325-330
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number3
StatePublished - Nov 3 1994



  • 5-HT receptor
  • 5-MeODMT (5-methoxy-N,N-dimethyltryptamine)
  • DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane)
  • MDMA (3,4-methylenedioxymethamphetamine)
  • Microdialysis
  • Neurotoxicity

ASJC Scopus subject areas

  • Pharmacology

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