Regulation of cortical and hippocampal 5-HT(1A) receptor function by corticosterone in GR+/- mice.
Regulation of cortical and hippocampal 5-HT(1A) receptor function by corticosterone in GR+/- mice.
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DOI：
10.1016/j.psyneuen.2009.08.015
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发表时间：
2010-04
影响因子：
3.7
通讯作者：
Gass, Peter
中科院分区：
文献类型：
--
作者：
Hensler, Julie G.;Vogt, Miriam A.;Gass, Peter
关键词：
我们本研究的目的是检查GR+/-小鼠前额叶皮质和海马中5-HT 1A受体的功能，这似乎是一种合适的抑郁症小鼠模型。通过测量5-HT 1A受体激动剂8-OH-DPAT（1 μM）刺激的[35 S]GTPγS结合来确定5-HT 1A受体功能，这表明受体激活G蛋白的能力。通过测量[3 H]8-OH-DPAT（2 nM）的结合测定5-HT 1A受体表达。我们观察到GR的组成性减少对5-HT 1A受体刺激的[35 S]GTPγS结合或5-HT 1A受体结合位点没有影响。对野生型小鼠进行皮质酮给药（10 mg/kg，sc，每日一次，持续21天）导致前额叶皮质中5-HT 1A受体功能降低[8-OH-DPAT刺激的[35 S]GTPγS结合（高于基础值的%），溶剂给药组：39±4.9;皮质酮给药组：17±2.8]，但海马中未出现这种情况。GR表达的组成性减少阻止了慢性皮质酮给药对额叶皮质5-HT 1A受体功能的下调。相比之下，GR+/−小鼠的皮质酮处理导致海马中5-HT 1A受体功能增加，在CA 23区达到统计学显著性[8-OH-DPAT刺激的[35 S]GTPγS结合（高于基础值的%），溶剂处理：41±9.7;皮质酮处理：94±23]。这些变化似乎是由高皮质酮水平和GR缺乏的综合作用引起的。虽然GR+/-小鼠没有表现出基线皮质酮的变化，但GR的组成性缺陷似乎在维持前额叶皮层和海马中5-HT 1A受体功能方面具有皮质酮升高的未掩盖的调节作用。
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 (1 μM), 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 (2 nM). 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 (10 mg/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.
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影响因子：
3.2
作者：
Hesen, W;Joels, M
通讯作者：
Joels, M
DOI：
10.1177/1359786806066063
发表时间：
2006-07-01
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Pariante, Carmine M
通讯作者：
Pariante, Carmine M
影响因子：
3.1
作者：
Drevets, Wayne C.;Thase, Michael E.;Mathis, Chester
通讯作者：
Mathis, Chester
影响因子：
5.3
作者：
Ridder, S;Chourbaji, S;Gass, P
通讯作者：
Gass, P
影响因子：
3.2
作者：
MEIJER, OC;DEKLOET, ER
通讯作者：
DEKLOET, ER