Differential regulation of 5-HT1A receptor-G protein interactions in brain following chronic antidepressant Administration

Julie G. Hensler

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Changes in 5-HT1A receptor function or sensitivity following chronic antidepressant treatment may involve changes in receptor-G protein interaction. We have examined the effect of chronic administration of the SSRI fluoxetine or the tricyclic antidepressant amitriptyline on 5-HT1A receptor-stimulated [35S]GTPγS binding in serotonergic cell body areas, and cortical and limbic structures using quantitative autoradiography. Treatment of rats with fluoxetine, but not amitriptyline, resulted in an attenuation of 5-HT1A receptor-stimulated [35S]GTPγS binding in the dorsal and median raphe nuclei. The binding of the antagonist radioligand [3H]MPPF to 5-HT1A receptor sites was not altered, suggesting that the observed changes in 5-HT1A receptor-stimulated [35S]GTPγS binding were not due to changes in receptor number. Thus, the desensitization of somatodendritic 5-HT1A autoreceptors in the dorsal and median raphe following chronic SSRI treatment appears to be due to a reduced capacity of the 5-HT1A receptor to activate G protein. By contrast, no significant change in postsynaptic 5-HT1A receptor-stimulated [35S]GTPγS binding was observed in any of the forebrain areas examined following chronic antidepressant treatment. Thus, changes in postsynaptic 5-HT1A receptor-mediated responses reported to follow chronic SSRI or tricyclic antidepressant administration most likely occur distal to receptor-G protein interaction, perhaps at the level of effector, or involving changes in neuronal function at the system or circuit level.

Original languageEnglish (US)
Pages (from-to)565-573
Number of pages9
JournalNeuropsychopharmacology
Volume26
Issue number5
DOIs
StatePublished - Apr 9 2002

Keywords

  • 5-HT receptor
  • 8-OH-DPAT
  • Amitriptyline
  • Fluoxetine
  • Quantitative autoradiography
  • [H]MPPF
  • [S]GTPgammaS

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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