Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release

Michael G. Bankson, Bryan K. Yamamoto

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

3,4,-Methylenedioxymethamphetamine (MDMA; 'ecstasy') acts at monoamine nerve terminals to alter the release and re-uptake of dopamine and 5-HT. The present study used microdialysis in awake rats to measure MDMA-induced changes in extracellular GABA in the ventral tegmental area (VTA), simultaneous with measures of extracellular dopamine (DA) in the nucleus accumbens (NAC) shell. (+)-MDMA (0, 2.5, 5 and 10 mg/kg, i.p.) increased GABA efflux in the VTA with a bell-shaped dose-response. This increase was blocked by application of TTX through the VTA probe. MDMA (5 mg/kg) increased 5-HT efflux in VTA by 1037% (p < 0.05). The local perfusion of the 5-HT2B/2C antagonist SB 206553 into the VTA reduced VTA GABA efflux after MDMA from a maximum of 229% to a maximum of 126% of basal values (p < 0.05), while having no effect on basal extracellular GABA concentrations. DA concentrations measured simultaneously in the NAC shell were increased from a maximum of 486% to 1320% (p < 0.05). The selective DA releaser d-amphetamine (AMPH) (4 mg/kg) also increased VTA GABA efflux (180%), did not alter 5-HT and increased NAC DA (875%) (p < 0.05), but the perfusion of SB 206553 into the VTA failed to alter these effects. These results suggest that MDMA-mediated increases in DA within the NAC shell are dampened by increases in VTA GABA subsequent to activation of 5-HT 2B/2C receptors in the VTA.

Original languageEnglish (US)
Pages (from-to)852-859
Number of pages8
JournalJournal of Neurochemistry
Volume91
Issue number4
DOIs
StatePublished - Nov 2004

Keywords

  • 3,4-methylenedioxymethamphetamine
  • Dopamine
  • Gamma amino butyric acid
  • Nucleus accumbens
  • Serotonin
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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