Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: Role of 5-HT 1A receptors

Roberto William Invernizzi, Giuseppina Sacchetti, Stefania Parini, Sabrina Acconcia, Rosario Samanin

Research output: Contribution to journalArticle

Abstract

1. Using in vivo intracerebral microdialysis in conscious, freely moving rats, we examined the effect of flibanserin, a potential antidepressant drug with high affinity for human 5-HT 1A receptors and four-50-fold lower affinity for 5-HT 2A and D 4 receptors, on basal extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain. 2. Flibanserin at 3 and 10 mg kg -1 significantly reduced extracellular 5-HT in the prefrontal cortex (by 30 and 45%) and dorsal raphe (35 and 44%), but had no effect on extracellular 5-HT in the ventral hippocampus. The 3 and 10 mg kg -1 doses raised extracellular NA to a similar extent in the prefrontal cortex (47 and 50%). In all, 10 mg kg -1 raised extracellular DA in the prefrontal cortex (63%) whereas 3 mg kg -1 had no significant effect. 3. Pretreatment with the selective 5-HT 1A receptor antagonist WAY100,635 (0.3 mg kg -1) 30 min before 10 mg kg -1 flibanserin completely antagonized the latter's effects on extracellular 5-HT, DA and NA in the prefrontal cortex. WAY100,635 by itself had no effect on cortical extracellular monoamines. 4. The results show that the stimulation of 5-HT 1A receptors plays a major role in the effect of flibanserin on brain extracellular 5-HT, DA and NA.

Original languageEnglish
Pages (from-to)1281-1288
Number of pages8
JournalBritish Journal of Pharmacology
Volume139
Issue number7
DOIs
Publication statusPublished - Aug 2003

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Keywords

  • 5-HT receptors
  • 5-HT receptors
  • 5-Hydroxytryptamine
  • Antidepressant drugs
  • Dopamine
  • Dorsal raphe
  • Microdialysis
  • Noradrenaline
  • Prefrontal cortex
  • Ventral hippocampus

ASJC Scopus subject areas

  • Pharmacology

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