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

Herbert Y. Meltzer; Michael Maes

doi:10.1016/0006-3223(95)00301-V

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

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Previous reports based on studies with serotonin (5-HT) precursors or direct acting agonists have suggested that postsynaptic 5-HT_1A and 5-HT_2A/5-HT_2C 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-HT_2A/5-HT_2C agonist, on the above hormones were studied in 11 normal men with and without pretreatment with pindolol, a 5-HT_1A 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-HT_2A or 5-HT_2C receptor activation, or both, despite 5-HT_1A inhibition; however, PRL secretion by MK-212 requires 5-HT_1A receptor availability as well as 5-HT_2A/5-HT_2C 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-HT_1A and 5-HT_2A/5-HT_2C receptors with regard to the 5-HT-dependent stimulation of PRL secretion.

Original language	English (US)
Pages (from-to)	310-318
Number of pages	9
Journal	Biological psychiatry
Volume	38
Issue number	5
DOIs	https://doi.org/10.1016/0006-3223(95)00301-V
State	Published - Sep 1 1995

Funding

Ihc research repot'led was supported in part by USPHS MH 41684, GCRC MOIRR00080 and grants from the Elisabeth Severance Prentiss, John f'ascall Sawyer Foundations,a nd the Michael Kaplen InvestigatorA ward to Dr. M. Mac~. Dr. H.Y. Mcltzer is the recipient of a USPHS Research Carecr Scientisl A,aard MH 47808. The secretarial assistance of Mrs. M. Maes and Ms. Lee Mason is greatly appreciated.

Keywords

5-HT
MK-212
pindolol
receptor
serotonin

ASJC Scopus subject areas

Biological Psychiatry

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10.1016/0006-3223(95)00301-V

Cite this

@article{520e44a4017444ad8e67d18d5e2c31c6,

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

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.",

keywords = "5-HT, MK-212, pindolol, receptor, serotonin",

author = "Meltzer, {Herbert Y.} and Michael Maes",

note = "Funding Information: Ihc research repot'led was supported in part by USPHS MH 41684, GCRC MOIRR00080 and grants from the Elisabeth Severance Prentiss, John f'ascall Sawyer Foundations,a nd the Michael Kaplen InvestigatorA ward to Dr. M. Mac~. Dr. H.Y. Mcltzer is the recipient of a USPHS Research Carecr Scientisl A,aard MH 47808. The secretarial assistance of Mrs. M. Maes and Ms. Lee Mason is greatly appreciated.",

year = "1995",

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day = "1",

doi = "10.1016/0006-3223(95)00301-V",

language = "English (US)",

volume = "38",

pages = "310--318",

journal = "Biological psychiatry",

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TY - JOUR

T1 - Effect of pindolol pretreatment on MK-212-induced plasma cortisol and prolactin responses in normal men

AU - Meltzer, Herbert Y.

AU - Maes, Michael

N1 - Funding Information: Ihc research repot'led was supported in part by USPHS MH 41684, GCRC MOIRR00080 and grants from the Elisabeth Severance Prentiss, John f'ascall Sawyer Foundations,a nd the Michael Kaplen InvestigatorA ward to Dr. M. Mac~. Dr. H.Y. Mcltzer is the recipient of a USPHS Research Carecr Scientisl A,aard MH 47808. The secretarial assistance of Mrs. M. Maes and Ms. Lee Mason is greatly appreciated.

PY - 1995/9/1

Y1 - 1995/9/1

N2 - 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.

AB - 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.

KW - 5-HT

KW - MK-212

KW - pindolol

KW - receptor

KW - serotonin

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U2 - 10.1016/0006-3223(95)00301-V

DO - 10.1016/0006-3223(95)00301-V

M3 - Article

C2 - 7495925

AN - SCOPUS:0029075949

SN - 0006-3223

VL - 38

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EP - 318

JO - Biological psychiatry

JF - Biological psychiatry

IS - 5

ER -

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

Abstract

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Keywords

ASJC Scopus subject areas

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