Regulation of Serotonin-1A Receptor Function in Inducible Brain-Derived Neurotrophic Factor Knockout Mice After Administration of Corticosterone

Julie G. Hensler, Tushar Advani, Lisa M. Monteggia

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background: We examined the effects of a forebrain-specific reduction in brain-derived neurotrophic factor (BDNF) on the regulation of serotonin-1A (5-HT1A) receptor function in serotonergic cell body areas as well as in limbic and cortical structures of mice chronically treated with corticosterone. Methods: 5-HT1A receptor function, at the level of receptor-G protein interaction, was assessed with quantitative autoradiography of [35S]GTPγS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT. 5-HT1A receptor number was assessed by measuring the binding of the antagonist radioligand [3H] WAY100635. Results: We observed a significant attenuation of 5-HT1A receptor function, in the absence of a change in receptor number, in the dorsal hippocampus of BDNF knockout versus control mice. There was no difference between control and BDNF knockout mice in 5-HT1A receptor number or function in the dorsal or median raphe nuclei or medial prefrontal cortex or anterior cingulate cortex. Corticosterone treatment of control mice decreased 5-HT1A receptor function in the dorsal and median raphe but not in hippocampus or frontal cortical areas. The regulation of 5HT1A receptor number or function in the dorsal and median raphe by corticosterone was lost in BDNF knockout mice. Conclusions: Attenuation of BDNF expression in forebrain regions produces differential effects on distinct 5-HT1A receptor populations and on the regulation of these receptor populations by corticosterone.

Original languageEnglish (US)
Pages (from-to)521-529
Number of pages9
JournalBiological Psychiatry
Volume62
Issue number5
DOIs
StatePublished - Sep 1 2007

Keywords

  • Dorsal raphe
  • [S]GTPγS binding
  • frontal cortex
  • hippocampus
  • median raphe
  • quantitative autoradiography

ASJC Scopus subject areas

  • Biological Psychiatry

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