Effect of pindolol pretreatment on MK-212-induced plasma cortisol and prolactin responses in normal men

Herbert Y. Meltzer*, Michael Maes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Previous reports based on studies with serotonin (5-HT) precursors or direct acting agonists have suggested that postsynaptic 5-HT1A and 5-HT2A/5-HT2C receptors may stimulate cortisol and prolactin (PRL) secretion in man. To further clarify the role of these receptors in the regulation of cortisol and PRL secretion in man, the effects of 6-chloro-2-(1-piperazinyl) pirazine (MK-212), a centrally acting direct 5-HT2A/5-HT2C agonist, on the above hormones were studied in 11 normal men with and without pretreatment with pindolol, a 5-HT1A partial agonist. MK-212 induced a significant increase in plasma concentrations of cortisol and PRL. The MK-212-induced response in plasma cortisol was not diminished by pindolol pretreatment, whereas the MK-212-induced PRL response was significantly inhibited by pindolol pretreatment. These data suggest that the MK-212-induced cortisol response may be mediated by 5-HT2A or 5-HT2C receptor activation, or both, despite 5-HT1A inhibition; however, PRL secretion by MK-212 requires 5-HT1A receptor availability as well as 5-HT2A/5-HT2C receptor activation, since blockade of the former appears to blunt the PRL responses to MK-212. These findings may be explained by postulating a cooperativity between 5-HT1A and 5-HT2A/5-HT2C receptors with regard to the 5-HT-dependent stimulation of PRL secretion.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalBiological psychiatry
Volume38
Issue number5
DOIs
StatePublished - Sep 1 1995

Keywords

  • 5-HT
  • 5-HT
  • 5-HT
  • 5-HT
  • MK-212
  • pindolol
  • receptor
  • serotonin

ASJC Scopus subject areas

  • Biological Psychiatry

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