Intranigral GR-113808, a selective 5-HT4 receptor antagonist, attenuates morphine-stimulated dopamine release in the rat striatum

Laura Pozzi, Luigia Trabace, Roberto Invernizzi, Rosario Samanin

Research output: Contribution to journalArticle

Abstract

GR-113808, a potent and selective 5-HT4 receptor antagonist, was infused through a microdialysis probe into the striatum and nucleus accumbens of awake rats, and basal and morphine-stimulated extracellular concentrations of dopamine (DA) were measured in these regions. At 1 and 10 μM GR-113808 did not effect the extracellular concentrations of DA in either region and 100 μM significantly reduced dialysate DA only in the striatum. A subcutaneous dose of 5 mg/kg morphine significantly raised extracellular concentrations of DA in the striatum and nucleus accumbens from 60 to 120 min after injection and the effect was not modified by 10 μM GR-113808 infused through the probe 20 min before and for 60 min after morphine. Bilateral injections of GR-113808 (1, 2.5 and 10 μg/0.5 μl) in the substantia nigra pars compacta did not affect dialysate DA in the striatum, except for a significant increase 120 min after the injection of 10 μg but the highest dose of GR-113808 prevented the increase of striatal DA caused by 5 mg/kg morphine s.c. The results suggest that 5-HT4 receptors in the substantia nigra modulate the activity of the dopaminergic nigrostriatal system only when the neurons are activated.

Original languageEnglish
Pages (from-to)265-268
Number of pages4
JournalBrain Research
Volume692
Issue number1-2
DOIs
Publication statusPublished - Sep 18 1995

Keywords

  • 5-HT receptor
  • Dopamine
  • GR-113808
  • Microdialysis
  • Nucleus accumbens
  • Serotonin
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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