Long-term impairment of anterograde axonal transport along fiber projections originating in the rostral raphe nuclei after treatment with fenfluramine or methylenedioxymethamphetamine

Brian T. Callahan, Branden J. Cord, George A. Ricaurte, Harry C. Dietz, Reed E. Pyeritz

Research output: Contribution to journalArticle

Abstract

To further evaluate the serotonin (5-HT) neurotoxic potential of substituted amphetamines, we used tritiated proline to examine anterograde transport along ascending axonal projections originating in the rostral raphe nuclei of animals treated 3 weeks previously with (±)fenfluramine (FEN, 10 mg/kg, every 2 h × 4 injections; i.p.) or (±)3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg, twice daily for 4 days; s.c.). The documented 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT, 75 μg; ICV; 30 min after pretreatment with pargyline, 50 mg/kg; i.p., and desipramine 25 mg/kg; i.p.), served as a positive control. Along with anterograde axonal transport, we measured two 5-HT axonal markers, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA). Prior treatment with FEN or MDMA led to marked reductions in anterograde transport of labeled material to various forebrain regions known to receive 5-HT innervation. These reductions were associated with lasting decrements in 5-HT axonal markers. In general, decreases in axonal transport were less pronounced than those in 5-HT and 5-HIAA. However, identical changes were observed after 5,7-DHT. These results further indicate that FEN and MDMA, like 5,7-DHT, are 5-HT neurotoxins.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalSynapse
Volume40
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • Anterograde transport
  • Fenfluramine
  • Methylenedioxymethamphetamine
  • Neurotoxicity
  • Serotonin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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