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

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

Research output: Contribution to journalArticle

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Abstract

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.

LanguageEnglish (US)
Pages325-330
Number of pages6
JournalEuropean Journal of Pharmacology
Volume264
Issue number3
DOIs
StatePublished - Nov 3 1994
Externally publishedYes

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Serotonin 5-HT2 Receptor Agonists
N-Methyl-3,4-methylenedioxyamphetamine
Dopamine
Serotonin
Methoxydimethyltryptamines
Corpus Striatum
Microdialysis
Brain

Keywords

  • 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

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. / Gudelsky, Gary A.; Yamamoto, Bryan; Frank Nash, J.

In: European Journal of Pharmacology, Vol. 264, No. 3, 03.11.1994, p. 325-330.

Research output: Contribution to journalArticle

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