Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats
Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats
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DOI：
10.1007/s00213-010-1948-y
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发表时间：
2010-10-01
影响因子：
3.4
通讯作者：
Kirouac, Gilbert J.
中科院分区：
文献类型：
--
作者：
Li, Yonghui;Li, Sa;Kirouac, Gilbert J.
解剖学研究表明，丘脑室旁核（PVT）支配前脑的区域，这些区域参与情绪行为的表达和调节，包括恐惧和焦虑。此外，PVT被含有食欲素-A（OXA）和食欲素-B（OXB）的纤维密集地支配，食欲素-A和食欲素-B是众所周知的对行为的唤醒作用的肽。我们研究了在PVT区域微量注射食欲素受体激动剂和拮抗剂是否会改变焦虑的表达，在高架十字迷宫中测量的大鼠的类似行为。我们报告说，在PVT区域微量注射OXA和OXB引起焦虑-类似的反应，如通过开放臂时间和进入的减少所指示的。此外，OXA和OXB产生的行为学指标的变化，表明焦虑状态。中枢给药促肾上腺皮质激素释放因子（CRF）或阿片κ受体拮抗剂可减弱PVT区域微量注射OXA产生的致焦虑作用。我们还提供了证据表明，内源性释放的食欲素作用于PVT产生焦虑，显示微量注射TCSOX 229，食欲素-2受体拮抗剂，在PVT地区减弱了焦虑的影响所产生的先前暴露于footshock stress.This研究表明，内源性释放的食欲素作用于PVT调节焦虑水平，通过涉及脑κ和CRF受体的机制。
Anatomical studies have shown that the paraventricular nucleus of the thalamus (PVT) innervates areas of the forebrain involved in the expression and regulation of emotional behaviors including fear and anxiety. In addition, the PVT is densely innervated by fibers containing orexin-A (OXA) and orexin-B (OXB), peptides that are well-known for their arousal effects on behavior.In this study, we investigate whether microinjections of orexin receptor agonists and antagonists in the PVT region alter expression of anxiety-like behaviors in the rat as measured in the elevated plus maze.We report that microinjections of OXA and OXB in the PVT region elicited anxiety-like response as indicated by a reduction in open arm time and entries. In addition, OXA and OXB produced changes in ethological measures indicative of an anxiety state. Central administrations of antagonists for corticotropin releasing factor (CRF) or the opioid kappa receptors attenuated the anxiogenic effects produced by microinjections of OXA in the PVT region. We also provide evidence that endogenously released orexins act at the PVT to produce anxiety by showing that microinjections of TCSOX229, an orexin-2 receptor antagonist, in the PVT region attenuated the anxiogenic effects produced by a previous exposure to footshock stress.This study indicates that endogenously released orexins act on the PVT to regulate anxiety levels through mechanisms involving the brain kappa and CRF receptors.