Ziegler D R, Cass W A, Herman J P
Department of Anatomy and Neurobiology, University of Kentucky Medical School, Chandler Medical Center, Lexington 40536-0084, USA.
J Neuroendocrinol. 1999 May;11(5):361-9. doi: 10.1046/j.1365-2826.1999.00337.x.
The locus coeruleus (LC) is a key brainstem region involved in arousal and is highly responsive to alerting/stressful stimuli, including those that activate the hypothalamic-pituitary-adrenocortical (HPA) axis. It is currently unclear whether the LC exerts any regulatory influence on the HPA axis and, consequently, on neuroendocrine responses to stress. The present studies were designed to test the hypothesis that the LC promotes HPA axis responses to acute and chronic stress. Adult male rats received bilateral (6-hydroxydopamine) lesions of the LC that produced severe cell loss in the LC and 80% depletion of noradrenaline in medial prefrontal cortex. Notably, lesions did not affect dopamine-beta-hydroxylase protein content in the parvocellular paraventricular nucleus (PVN), indicating a lack of collateral damage to other ascending noradrenergic pathways. LC lesions significantly reduced peak adrenocorticotropic hormone (ACTH) and corticosterone responses to 30 min acute restraint stress. However, LC lesions did not significantly attenuate neuroendocrine or other physiological responses to a 4-week chronic variable stress regimen. LC lesions did not substantially affect basal concentrations of plasma corticosterone or corticotropin-releasing hormone mRNA expression in the hypothalamic paraventricular nucleus following chronic stress. We conclude that the LC is a HPA-excitatory brain region, promoting neuroendocrine and physiological responses primarily to acute stress. However, a potential role for the LC in the induction of HPA axis hyperactivity following chronic stress can not be ruled out.
蓝斑（LC）是参与觉醒的关键脑干区域，对警报/应激刺激高度敏感，包括那些激活下丘脑 - 垂体 - 肾上腺皮质（HPA）轴的刺激。目前尚不清楚蓝斑是否对HPA轴以及因此对压力的神经内分泌反应施加任何调节影响。本研究旨在检验蓝斑促进HPA轴对急性和慢性应激反应的假设。成年雄性大鼠接受蓝斑的双侧（6 - 羟基多巴胺）损伤，这导致蓝斑严重细胞损失以及内侧前额叶皮质中去甲肾上腺素耗竭80％。值得注意的是，损伤并未影响小细胞室旁核（PVN）中多巴胺 - β - 羟化酶蛋白含量，表明对其他上行去甲肾上腺素能通路没有附带损害。蓝斑损伤显著降低了对30分钟急性束缚应激的促肾上腺皮质激素（ACTH）峰值和皮质酮反应。然而，蓝斑损伤并未显著减弱对4周慢性可变应激方案的神经内分泌或其他生理反应。慢性应激后，蓝斑损伤对血浆皮质酮的基础浓度或下丘脑室旁核中促肾上腺皮质激素释放激素mRNA表达没有实质性影响。我们得出结论，蓝斑是一个HPA兴奋性脑区，主要促进对急性应激的神经内分泌和生理反应。然而，不能排除蓝斑在慢性应激后诱导HPA轴功能亢进中的潜在作用。
