Enhancement of fluoxetine-dependent increase of extracellular serotonin (5-HT) levels by (-)-pindolol, an antagonist at 5-HT1A receptors

Laura J. Dreshfield, David T. Wong, Kenneth W. Perry, Eric Engleman

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The somatodendritic 5-HT1A autoreceptor is known to regulate activity of 5-HT neurons and consequently 5-HT release. Administration of a selective 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i.p.) increased extracellular 5-HT levels in rat hypothalamus up to 260 percent of basal levels. (-)-Pindolol, an antagonist at the somatodendritic 5-HT1A autoreceptor, dose-dependently (1, 3 and 5 mg/kg, s.c.) potentiated the fluoxetine dependent increase up to 458 percent of basal 5-HT levels for approximately 1.5 hours. Continuous infusion of (±)-pindolol at 30 mg/kg/h s.c. enhanced the fluoxetine dependent elevation of extracellular 5-HT concentrations in hypothalamus up to 464 percent of basal levels and lasted for 3 hours. Thus, the combination of 5-HT uptake inhibition with antagonism at the somatodendritic 5-HT1A autoreceptor can enhance 5-HT release to levels beyond those achieved with uptake inhibition alone. The present findings are consistent with the hypothesis that blockade of somatodendritic 5-HT1A autoreceptors removes the inhibitory effect exerted by the elevated 5-HT levels resulting from uptake inhibition.

Original languageEnglish (US)
Pages (from-to)557-562
Number of pages6
JournalNeurochemical Research
Volume21
Issue number5
DOIs
StatePublished - May 1996
Externally publishedYes

Fingerprint

Pindolol
Receptor, Serotonin, 5-HT1A
Fluoxetine
Serotonin
Autoreceptors
Hypothalamus
Serotonin Uptake Inhibitors
Neurons
Rats

Keywords

  • fluoxetine
  • hypothalamus
  • microdialysis
  • pindolol
  • Serotonin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry
  • Neuroscience(all)

Cite this

Enhancement of fluoxetine-dependent increase of extracellular serotonin (5-HT) levels by (-)-pindolol, an antagonist at 5-HT1A receptors. / Dreshfield, Laura J.; Wong, David T.; Perry, Kenneth W.; Engleman, Eric.

In: Neurochemical Research, Vol. 21, No. 5, 05.1996, p. 557-562.

Research output: Contribution to journalArticle

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