Mice Lacking Adenylyl Cyclase-5 Cope Badly With Repeated Restraint Stress
Mice Lacking Adenylyl Cyclase-5 Cope Badly With Repeated Restraint Stress
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DOI：
10.1002/jnr.22119
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发表时间：
2009-10-01
影响因子：
4.2
通讯作者：
Han, Pyung-Lim
中科院分区：
文献类型：
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作者：
Kim, Kyoung-Shim;Han, Pyung-Lim
对急性应激的生理反应伴随着下丘脑-垂体-肾上腺(HPA)系统的激活。已知许多大脑区域在应激反应中调节HPA轴的激活，但HPA轴上游的详细神经回路和信号系统仍需进一步探索。5型腺苷酸环化酶(AC5)在背侧纹状体和伏隔核中高度集中，与奖赏和应激相关的行为有关。AC5(-/-)小鼠暴露在每天2小时的束缚应激中，仅持续3-5天，表现出较差的压力应对反应，包括体重严重减轻、皮毛状况不佳、呼吸困难和冰冻行为。与AC5(+/+)小鼠相比，AC5(-/-)小鼠在2小时应激期间的血浆皮质酮水平升高。然而，皮质酮受体拮抗剂RU486和CRH受体拮抗剂NBI27914都不能阻止他们糟糕的应激应对，而在束缚应激之前给予GABA(A)受体变构调节剂地西潘或D1多巴胺受体拮抗剂SCH23390改变了他们对应激AC5(+/+)小鼠的应激应对反应。应激触发的c-Fos表达在AC5(-/-)背侧纹状体完全钝化。这些结果表明，AC5相关的信号系统和神经网络参与了焦虑和压力应对反应的调节。(C)2009年Wiley-Liss，Inc.
Physiological responses to acute stress proceed with the activation of the hypothalamus-pituitary-adrenal gland (HPA) system. Many brain regions are known to modulate the HPA axis activation in stress responses, but the detailed neural circuits and signaling system in the upstream of the HPA axis have to be explored further. Type 5 adenylyl cyclase (AC5) is highly concentrated in the dorsal striatum and nucleus accumbens, which are implicated in reward and stress-related behavior. AC5(-/-) mice exposed to daily 2-hr restraint stress for only 3-5 days showed poor stress-coping responses, including severe body weight loss, poor coat condition, respiratory difficulties, and freezing behavior. Plasma corticosterone levels during 2-hr stress sessions increased in AC5(-/-) mice compared with those of AC5(+/+) mice. However, neither the corticosterone receptor antagonist RU486 nor the CRH receptor antagonist NBI27914 blocked their poor stress coping, whereas the administration of the GABA(A) receptor allosteric modulator diazepam or the D1 dopamine receptor antagonist SCH23390 prior to restraint stress sessions changed their stress-coping response to the stressed AC5(+/+) mouse level. Stress-triggered c-Fos expression was completely blunted in the dorsal striaturn of AC5(-/-). These results suggest that the AC5-associated signal system and neural network are involved in the regulation of anxiety and stress-coping response. (C) 2009 Wiley-Liss, Inc.