In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function

Paul D. Callaghan, W. Anthony Owens, Martin A. Javors, Teresa A. Sanchez, David J. Jones, Rodney J. Irvine, Lynette C. Daws

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [3H]5-HT uptake into synaptosomes and [3H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions.

Original languageEnglish (US)
Pages (from-to)617-627
Number of pages11
JournalJournal of neurochemistry
Volume100
Issue number3
DOIs
StatePublished - Feb 2007

Keywords

  • 3, 4-methylenedioxymethamphetamine
  • Chronoamperometry
  • Neurodegeneration
  • Para-methoxyamphetamine
  • Serotonin
  • Serotonin transporter

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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