Modulation of methylenedioxymethamphetamine-induced striatal dopamine release by the interaction between serotonin and γ-aminobutyric acid in the substantia nigra

B. K. Yamamoto, J. F. Nash, G. A. Gudelsky

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

The effects of the amphetamine analog, 3,4-methylenedioxymethamphetamine (MDMA) were compared to the effects of d-amphetamine on the in vivo release of dopamine and τ-aminobutyric acid (GABA) in the striatum and substantia nigra. The brain region-dependent role of the 5-HT2 receptors in the striatum and substantia nigra in regulating MDMA-induced dopamine and GABA release also was studied. Changes in the extracellular concentration of dopamine, 5-HT and GABA were measured simultaneously in the awake rat by in vivo microdialysis. The increase in striatal dopamine produced by systemic administration of MDMA was attenuated by infusion of TTX into the striatum. Infusion of the 5-HT(2A/2C) antagonist ritanserin into the striatum or the ipsilateral substantia nigra also significantly attenuated MDMA-induced dopamine release in the striatum. At the doses used in this study, MDMA but not d-amphetamine increased the extracellular concentrations of 5-HT and decreased GABA efflux in the substantia nigra. The ability of MDMA to decrease nigral GABA efflux also was blocked by the local infusion of ritanserin into either the substantia nigra or the striatum. Overall, these data provide evidence that MDMA increases dopamine release partly through an impulse-mediated mechanism. Furthermore, this increase in striatal dopamine efflux produced by MDMA is regulated, in part, by 5-HT(2A/2C) receptors in the striatum and the substantia nigra and ultimately by GABAergic input into the substantia nigra.

Original languageEnglish (US)
Pages (from-to)1063-1070
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume273
Issue number3
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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