Regulation of cortical and hippocampal 5-HT1A receptor function by corticosterone in GR+/- mice

Julie G. Hensler, Miriam A. Vogt, Peter Gass

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Our objective in the present study was to examine 5-HT1A receptor function in prefrontal cortex and hippocampus of GR+/- mice, which appear to be an appropriate murine model of depression. 5-HT1A receptor function was determined by measuring [35S]GTPγS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT (1μM), an indication of the capacity of the receptor to activate G proteins. 5-HT1A receptor expression was determined by measuring the binding of [3H]8-OH-DPAT (2nM). We observed no effect of the constitutive reduction in GR on 5-HT1A receptor-stimulated [35S]GTPγS binding or 5-HT1A receptor binding sites. Corticosterone treatment (10mg/kg, sc once daily for 21 days) of wild-type mice resulted in a decrease in 5-HT1A receptor function in prefrontal cortex [8-OH-DPAT-stimulated [35S]GTPγS binding (% above basal), vehicle-treated: 39±4.9; corticosterone-treated: 17±2.8], but not in hippocampus. The constitutive reduction in GR expression prevented the down-regulation of 5-HT1A receptor function in frontal cortex by chronic corticosterone administration. In contrast, corticosterone treatment of GR+/- mice resulted in an increase in 5-HT1A receptor function in hippocampus which reached statistical significance in CA2/3 region [8-OH-DPAT-stimulated [35S]GTPγS binding (% above basal), vehicle-treated: 41±9.7; corticosterone-treated: 94±23]. These changes seem to be evoked by a combined effect of high corticosterone levels and GR deficiency. Although GR+/- mice do not exhibit changes in baseline corticosterone, the constitutive deficiency in GR appears to have unmasked regulatory effects of elevated corticosterone in the maintenance of 5-HT1A receptor function in prefrontal cortex and hippocampus.

Original languageEnglish (US)
Pages (from-to)469-474
Number of pages6
JournalPsychoneuroendocrinology
Volume35
Issue number3
DOIs
StatePublished - Apr 2010

Keywords

  • Corticosterone
  • Glucocorticoid receptor
  • Major depression
  • Quantitative autoradiography
  • Serotonin
  • [S]GTPγS binding

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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