| Co-Investigator(Kenkyū-buntansha) |
SHIMOYAMA Megumi Chiba University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究院, 講師 (10206253)
NAKAMURA Akira Chiba University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 助手 (40343090)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
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.
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