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

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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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
Volume66
Issue number2
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

LY 206130
Receptor, Serotonin, 5-HT1A
Hypothalamus
Rats
Serotonin
Norepinephrine
Dopamine
Serotonin 5-HT1 Receptor Antagonists
3,4-Dihydroxyphenylacetic Acid
Autoreceptors
Hydroxyindoleacetic Acid
Serotonin Uptake Inhibitors
Duloxetine Hydrochloride

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Antagonism of serotonin 5-HT1A receptors potentiates the increases in extracellular monoamines induced by duloxetine in rat hypothalamus. / Engleman, Eric; Robertson, David W.; Thompson, Dennis C.; Perry, Kenneth W.; Wong, David T.

In: Journal of Neurochemistry, Vol. 66, No. 2, 02.1996, p. 599-603.

Research output: Contribution to journalArticle

Engleman, Eric ; Robertson, David W. ; Thompson, Dennis C. ; Perry, Kenneth W. ; Wong, David T. / Antagonism of serotonin 5-HT1A receptors potentiates the increases in extracellular monoamines induced by duloxetine in rat hypothalamus. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 2. pp. 599-603.
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