ADAPTATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS TO CHRONIC ETHANOL STRESS
ADAPTATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS TO CHRONIC ETHANOL STRESS
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DOI：
10.1159/000125632
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发表时间：
1990-11-01
影响因子：
4.1
通讯作者：
MCEWEN, BS
中科院分区：
文献类型：
--
作者：
SPENCER, RL;MCEWEN, BS
慢性乙醇应激改变下丘脑-垂体-肾上腺（HPA）轴功能的能力进行了评估，其方式与以前报道的其他慢性应激治疗相似。给雄性Sprague-Dawley或Long-Evans大鼠注射乙醇（1- 4g/kg i. p.，20%v/v的生理盐水）导致血清皮质酮水平快速和大幅上升，其中最大水平由2g/kg乙醇剂量产生。较高剂量的乙醇并没有增加最大皮质酮的反应以上所产生的2克/公斤乙醇，但他们延长了峰值响应的持续时间。长期乙醇应激处理（1-3周）产生了HPA轴过度刺激的迹象，如肾上腺肥大和胸腺退化所示。然而，HPA轴适应慢性乙醇治疗。在治疗的最后一天，皮质酮对乙醇的反应显著低于治疗的第一天，尽管两种测量时的血清乙醇水平相当。在慢性乙醇处理的大鼠中也没有糖皮质激素分泌负反馈控制受损的迹象。他们表现出正常的皮质酮反应1小时的约束和正常关闭的压力反应。也没有下调I型或II型肾上腺皮质类固醇受体在慢性乙醇应激处理的大鼠海马。这些研究说明了HPA轴的能力，以适应慢性刺激的乙醇应激，同时保持正常的皮质酮应激反应，这提供了一些深入了解糖皮质激素升高的程度和持续时间，可能是必要的产生适应不良的HPA轴。
The ability of chronic ethanol stress to alter hypothalamic-pituitary-adrenal (HPA) axis function in a manner similar to that previously reported for other chronic stress treatments was evaluated. Injection of male Sprague-Dawley or Long-Evans rats with ethanol (1-4 g/kg i.p., 20% v/v in saline) resulted in a rapid and large rise in serum corticosterone levels with maximal levels produced by a dose of 2 g/kg ethanol. Higher doses of ethanol did not increase the maximum corticosterone response above those produced by 2 g/kg ethanol but they extended the duration of the peak response. Chronic treatment with ethanol stress (1-3 weeks) produced signs of hyperstimulation of the HPA axis as indicated by adrenal hypertrophy and thymus involution. There was, however, adaptation of the HPA axis to the chronic ethanol treatment. The corticosterone response to ethanol on the last day of treatment was significantly less than on the first day of treatment, even though serum ethanol levels at the time of both measures were equivalent. There also were no signs of impaired negative feedback control of glucocorticoid secretion in the chronic-ethanol-treated rats. They exhibited a normal corticosterone response to 1 h of restraint and a normal shut-off of the stress response. There was also no down-regulation of type I or type II adrenal steroid receptors in the hippocampus of chronic ethanol-stress-treated rats. These studies illustrate the ability of the HPA axis to adapt to chronic stimulation by ethanol stress while maintaining a normal corticosterone stress response and this offers some insight into the degree and duration of glucocorticoid elevation that may be necessary to produce a maladaptation of the HPA axis.