Dallman Mary F, Pecoraro Norman C, La Fleur Susanne E, Warne James P, Ginsberg Abigail B, Akana Susan F, Laugero Kevin C, Houshyar Hani, Strack Alison M, Bhatnagar Seema, Bell Mary E
University of California at San Francisco, San Francisco, CA 94143-0444, USA.
Prog Brain Res. 2006;153:75-105. doi: 10.1016/S0079-6123(06)53004-3.
Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a chronic stressor, the steroids act in brain in a feed-forward fashion to recruit a stress-response network that biases ongoing autonomic, neuroendocrine, and behavioral outflow as well as responses to novel stressors. We review evidence for the role of glucocorticoids in activating the central stress-response network, and for mediation of this network by corticotropin-releasing factor (CRF). We briefly review the effects of CRF and its receptor antagonists on motor outflows in rodents, and examine the effects of glucocorticoids and CRF on monoaminergic neurons in brain. Corticosteroids stimulate behaviors that are mediated by dopaminergic mesolimbic "reward" pathways, and increase palatable feeding in rats. Moreover, in the absence of corticosteroids, the typical deficits in adrenalectomized rats are normalized by providing sucrose solutions to drink, suggesting that there is, in addition to the feed-forward action of glucocorticoids on brain, also a feedback action that is based on metabolic well being. Finally, we briefly discuss the problems with this network that normally serves to aid in responses to chronic stress, in our current overindulged, and underexercised society.
糖皮质激素对下丘脑-垂体-肾上腺（HPA）轴应激诱导的活动具有抑制或致敏作用，这取决于给药后的时间、类固醇的浓度以及是否存在并发应激源输入。当高浓度糖皮质激素与慢性应激源同时存在时，这些类固醇以一种前馈方式作用于大脑，从而激活一个应激反应网络，该网络会使正在进行的自主神经、神经内分泌和行为输出以及对新应激源的反应产生偏差。我们综述了糖皮质激素在激活中枢应激反应网络中的作用以及促肾上腺皮质激素释放因子（CRF）对该网络的介导作用的相关证据。我们简要回顾了CRF及其受体拮抗剂对啮齿动物运动输出的影响，并研究了糖皮质激素和CRF对大脑中单胺能神经元的影响。皮质类固醇刺激由多巴胺能中脑边缘“奖赏”通路介导的行为，并增加大鼠对美味食物的摄取。此外，在没有皮质类固醇的情况下，给肾上腺切除的大鼠提供蔗糖溶液饮用可使其典型缺陷恢复正常，这表明除了糖皮质激素对大脑的前馈作用外，还存在一种基于代谢健康的反馈作用。最后，我们简要讨论了在当前过度放纵和缺乏运动的社会中，这个通常有助于应对慢性应激的网络所存在的问题。
