Neural mechanisms and transmitters of the defense response against stress

应激源不仅会引起认知、情绪和行为的改变，还会引起自主神经的改变。尽管对这种自主神经变化背后的神经回路的研究表明，下丘脑参与了对应激源的防御反应，但这种多方面和协调反应中的神经递质尚未被揭示。我们先前已经证明，在食欲素前体基因敲除小鼠(ORX-KO)中，防御反应的一些特征，如动脉血压(AP)、心率(HR)和通气量的增加被减弱。在这里，我们检查了在食欲素神经元消融小鼠(ORX/ATX-TG)中是否存在同样的情况。此外，我们还检查了防御反应的其他特征：骨骼肌血管扩张和压力感受器反射的移位。在麻醉和清醒状态下，ORX/ATX-TG的基础AP均比WT低约20 mm Hg，ORX-KO也是如此。使用α阻滞剂治疗后，AP的差异消失，但不使用β阻滞剂，这表明交感血管收缩药流出减少。与野生型对照组(WT)相比，乌拉坦麻醉ORX/ATX-TG组的腹膜周围区(PFA)的AP、HR、通气量和骨骼肌血管扩张的增加较小且持续时间较短。此外，在清醒的ORX/ATX-TG中，空气喷射应激引起的AP和HR升高被减弱。在用β阻断剂阿替洛尔预处理后，刺激PFA可抑制苯肾上腺素引起的WT心动过缓。这演示了压力感受器反射的重置。然而，在ORX/ATX-TG中，没有观察到明显的抑制作用。本研究进一步支持了我们的假设，即PFA中含有食欲素的神经元在激活防御反应的多条传出通路时起着主开关的作用，同时也是基础AP的调节因子。

Stressor induces not only cognitive, emotional and behavioral changes but also autonomic changes. Although research on the neural circuits underlying such autonomic changes has implicated the hypothalamus in the defense response against stressors, neurotransmitters in this multifaceted and coordinated response have not been revealed. We have previously shown that some features of the defense response, such as increases in arterial blood pressure (AP), heart rate (HR), and ventilation were attenuated in prepro-orexin knockout mice (ORX-KO). Here we examined whether the same was true in orexin neuron-ablated mice (ORX/ATX-Tg). In addition, we examined the other features of the defense response ; skeletal muscular vasodilation and shift of baroreceptor reflex. Both in anesthetized and conscious conditions, basal AP in ORX/ATX-Tg was significantly lower by 〜20 mmHg than that in WT, as was the case in ORX-KO. The difference in AP was disappeared after treatment with an α-blacker but not with β-blocker, indicating lower sympathetic vasoconstrictor outflow. Stimulation of the perifomical area (PFA) in urethane-anesthetized ORX/ATX-Tg elicited smaller and shorter-lasting increases in AP, HR, and ventilation and skeletal muscle vasodilation than those in the wild-type controls (WT). In addition, air jet stress-induced elevations of AP and HR were attenuated in conscious ORX/ATX-Tg. After pretreatment with a β-blocker, atenolol, stimulation of PFA suppressed phenylephrine induced bradycardia in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX-Tg, however, no significant suppression was observed. The present study provided further support for our hypothesis that orexin-containing neurons in PFA play a role as a master switch to activate multiple efferent pathways of the defense response and also operate as a regulator of basal AP.