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  • Title: Regulation of cortical and hippocampal 5-HT(1A) receptor function by corticosterone in GR+/- mice.
    Author: Hensler JG, Vogt MA, Gass P.
    Journal: Psychoneuroendocrinology; 2010 Apr; 35(3):469-74. PubMed ID: 19766402.
    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.
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