Sandi Carmen, Cordero M Isabel, Ugolini Annarosa, Varea Emilio, Caberlotto Laura, Large Charles H
Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.
Eur J Neurosci. 2008 Nov;28(9):1836-48. doi: 10.1111/j.1460-9568.2008.06451.x.
The basolateral nucleus of the amygdala (BLA) plays a key role in emotional arousal and anxiety, and expresses high levels of corticotropin-releasing factor receptor (CRFR)1. In rat brain slices, we have recently shown that afferent activation of the BLA is increased following application of exogenous corticotropin-releasing factor (CRF). Here we examined the impact of chronic unpredictable stress (CUS) on this effect of CRF and whether blockade of CRFR1 could prevent stress-induced changes in the electrophysiological response, the animal's behavior and in cell proliferation in the hippocampus. The behavior of the rats was monitored via a series of tests that formed part of the CUS. Electrophysiological measures of the BLA response to CRF, cell proliferation in the dentate gyrus and the expression of CRF and CRFR1 mRNA in amygdaloid nuclei were determined ex vivo after completion of the CUS. CRF-induced potentiation of afferent activation of the BLA was reduced in rats exposed to CUS, an effect that was inhibited by chronic antagonism of CRFR1. Furthermore, the reduction in BLA response to CRF was correlated with the anxiety trait of the animals, determined prior to initiation of the CUS. These results implicate CRFR1 in chronic stress-induced alterations in amygdala function and behavior. Furthermore, they show that CRFR1 antagonists can prevent changes induced by chronic stress, in particular in those animals that are highly anxious.
杏仁核基底外侧核（BLA）在情绪唤醒和焦虑中起关键作用，并表达高水平的促肾上腺皮质激素释放因子受体（CRFR）1。在大鼠脑片中，我们最近发现，应用外源性促肾上腺皮质激素释放因子（CRF）后，BLA的传入激活增加。在此，我们研究了慢性不可预测应激（CUS）对CRF这种作用的影响，以及阻断CRFR1是否能预防应激诱导的电生理反应、动物行为和海马体细胞增殖的变化。通过CUS的一系列测试来监测大鼠的行为。在完成CUS后，离体测定BLA对CRF反应的电生理指标、齿状回中的细胞增殖以及杏仁核中CRF和CRFR1 mRNA的表达。暴露于CUS的大鼠中，CRF诱导的BLA传入激活增强作用减弱，而这种作用可被CRFR1的慢性拮抗作用所抑制。此外，BLA对CRF反应的降低与CUS开始前测定的动物焦虑特质相关。这些结果表明CRFR1参与了慢性应激诱导的杏仁核功能和行为改变。此外，它们表明CRFR1拮抗剂可以预防慢性应激诱导的变化，特别是在那些高度焦虑的动物中。
