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Neurochemical Research

, Volume 21, Issue 5, pp 557–562 | Cite as

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 A. Engleman
Original Articles

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.

Key Words

Serotonin hypothalamus fluoxetine pindolol microdialysis 

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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Laura J. Dreshfield
    • 1
  • David T. Wong
    • 1
  • Kenneth W. Perry
    • 1
  • Eric A. Engleman
    • 1
  1. 1.Lilly Research Laboratories, Eli Lilly and CompanyLilly Corporate CenterIndianapolis

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