Antagonism of serotonin 5-HT1A receptors potentiates the increases in extracellular monoamines induced by duloxetine in rat hypothalamus

Eric A. Engleman, David W. Robertson, Dennis C. Thompson, Kenneth W. Perry, David T. Wong

Research output: Contribution to journalArticle

35 Scopus citations


In the current study we examined the effects of coadministration of a serotonin 5-HT1A antagonist, (±)-1-(1H-indol-4-yloxy)-3-(cyclohexylamino)-2-propanol maleate (LY 206130), and a dual 5-HT and norepinephrine (NE) uptake inhibitor, duloxetine, on extracellular levels of NE, 5-HT, dopamine (DA), 5-hydroxyindoleacetic acid, and 3,4-dihydroxyphenylacetic acid in rat hypothalamus microdialysates. LY 206130 (3.0 mg/kg, s.c.) alone significantly increased NE and DA levels by 60 and 34%, respectively, without affecting 5-HT levels. Duloxetine administration at 4.0 mg/kg, i.p. alone produced no significant changes in levels of 5-HT, NE, or DA. In contrast, when LY 206130 and duloxetine were coadministered at 3.0 mg/kg, s.c. and 4.0 mg/kg, i.p., respectively, 5-HT, NE, and DA levels increased to 5.7-, 4.8-, and threefold over their respective basal levels. These data demonstrate that antagonism of somatodendritic 5-HT1A autoreceptors and concomitant inhibition of 5-HT and NE uptake with duloxetine may promote synergistic increases in levels of extracellular 5-HT, NE, and DA in hypothalamus of conscious, freely moving rats.

Original languageEnglish (US)
Pages (from-to)599-603
Number of pages5
JournalJournal of Neurochemistry
Issue number2
StatePublished - Feb 1 1996
Externally publishedYes


  • 5-HT antagonist
  • 5-HT receptors
  • Duloxetine
  • Extracellular monoamines
  • Hypothalamus
  • LY 206130

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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