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Psychoneuroendocrinology. 2010 Apr;35(3):469-74. doi: 10.1016/j.psyneuen.2009.08.015. Epub 2009 Sep 18.

Regulation of cortical and hippocampal 5-HT(1A) receptor function by corticosterone in GR+/- mice.

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  • 1Department of Pharmacology, MC 7764, University of Texas Health Science Center-San Antonio, San Antonio, TX 78229-3900, United States. hensler@uthscsa.edu

Abstract

Our objective in the present study was to examine 5-HT(1A) receptor function in prefrontal cortex and hippocampus of GR+/- mice, which appear to be an appropriate murine model of depression. 5-HT(1A) receptor function was determined by measuring [(35)S]GTPgammaS binding stimulated by the 5-HT(1A) receptor agonist 8-OH-DPAT (1 microM), an indication of the capacity of the receptor to activate G proteins. 5-HT(1A) receptor expression was determined by measuring the binding of [(3)H]8-OH-DPAT (2 nM). We observed no effect of the constitutive reduction in GR on 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding or 5-HT(1A) receptor binding sites. Corticosterone treatment (10mg/kg, sc once daily for 21 days) of wild-type mice resulted in a decrease in 5-HT(1A) receptor function in prefrontal cortex [8-OH-DPAT-stimulated [(35)S]GTPgammaS 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-HT(1A) receptor function in frontal cortex by chronic corticosterone administration. In contrast, corticosterone treatment of GR+/- mice resulted in an increase in 5-HT(1A) receptor function in hippocampus which reached statistical significance in CA2/3 region [8-OH-DPAT-stimulated [(35)S]GTPgammaS 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-HT(1A) receptor function in prefrontal cortex and hippocampus.

PMID:
19766402
PMCID:
PMC3816533
DOI:
10.1016/j.psyneuen.2009.08.015
[PubMed - indexed for MEDLINE]
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