ADRENOCORTICAL ACTIVATION IN ALCOHOLICS DURING CHRONIC DRINKING *
ADRENOCORTICAL ACTIVATION IN ALCOHOLICS DURING CHRONIC DRINKING *
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长期饮酒期间饮酒者的肾上腺皮质激活 *
DOI：
10.1111/j.1749-6632.1973.tb28251.x
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发表时间：
1973
影响因子：
5.2
通讯作者：
P. Stokes
中科院分区：
文献类型：
--
作者：
P. Stokes
酒精对垂体肾上腺皮质功能的影响仅在最近几年才被探索，借助生化技术，可以直接测量血浆肾上腺皮质类固醇水平和尿中肾上腺皮质类固醇及其代谢物的排泄。然而，间接测量表明，酒精确实影响垂体肾上腺皮质功能。自从Santisteban和Swinyard观察到，在完整的胸腺萎缩的动物中，酒精给药后出现了胸腺溶解反应以来，反映肾上腺皮质激活的反应25并不是酒精的直接影响，因为在肾上腺切除的动物中，酒精并没有改变对各种剂量的氢化可的松的胸腺溶解反应。smith 26,27以及Forbes和Duncan7随后表明，在大鼠中，通过肾上腺皮质抗坏血酸消耗来评估，腹腔内酒精注射产生的肾上腺皮质激活依赖于完整的垂体和ACTH释放。酒精不增强外源性给药促肾上腺皮质激素对垂体切除动物的肾上腺皮质刺激作用。然而，这些实验并没有阐明酒精激活垂体肾上腺皮质的模式。关于慢性饮酒期间下丘脑-垂体-肾上腺皮质（HPAC）功能的数据缺乏，但关于酒精对动物和人类HPAC功能的急性影响有相当多的数据。因此，简要回顾一下酒精对HPAC功能影响的动物和人类数据是合适的。Ellis是第一个通过增加酒精剂量直接测量血浆皮质酮水平来显示进行性肾上腺皮质激活的大鼠在给予最低剂量（0.5 mg/kg体重）时，他报告没有“可察觉的”中枢神经系统的抑制，但发现血浆皮质酮水平有轻微的增加。这些数据表明，至少在大鼠中，饮酒后脑垂体肾上腺皮质可能会激活，而不会出现可检测到的行为改变。最近，对麻醉动物的实验帮助将疼痛的影响从酒精注射或酒精引起的行为改变中分离出来，从酒精对激活垂体肾上腺皮质系统的直接影响中分离出来。因此，Ellis在一系列揭示性的实验中证实了Czaja和Kalant的发现，他们提出了一些类似的数据，表明在腹腔局部麻醉预处理的大鼠中，皮质酮对酒精的反应没有抑制作用。大剂量戊巴比妥可抑制HPAC对盐酸戊巴比妥的反应。~ Ellis证明，大鼠戊巴比妥麻醉（50 mg/kg）使皮质酮对麻醉后10分钟给予酒精（2 mg/kg）的反应降低到未麻醉动物反应的50%左右。这些数据是重要的，因为它们是第一个支持酒精本身诱导肾上腺激活的假设，而没有作为必要的前兆可检测到的行为改变。吗啡已经被证明对HPAC系统有阻断作用
The effect of alcohol on pituitary adrenocortical function has been explored only in recent years with the aid of biochemical techniques that allow a direct measure of plasma adrenocorticoid steroid levels and urinary excretion of adrenocortical steroids and their metabolites. However, it has been made evident by indirect measures that alcohol does affect pituitary adrenocortical function ever since Santisteban and Swinyard observed a thymolytic response after alcohol administration in intact Atrophy of the thymus, a response reflecting adrenocortical activation25 was not a direct effect of alcohol, since alcohol did not change the thymolytic response to various doses of hydrocortisone in adrenalectomized animals. Smith26,27 and Forbes and Duncan7 subsequently showed that, in rats, the adrenocortical activation produced by intraperitoneal alcohol injection, as assessed by adrenocortical ascorbic acid depletion, was dependent on an intact pituitary gland and ACTH release. Alcohol did not potentiate the adrenocortical stimulating effect of exogenously administered ACTH in hypophysectomized animals. However, these experiments throw no light on the mode of pituitary adrenocortical activation by alcohol. There is a dearth of data on hypothalamic-pituitary-adrenocortical (HPAC) function during chronic drinking, but there are considerable data on acute effects of alcohol on HPAC function in animals and humans. Therefore, a brief review of the animals and human data regarding effects of alcohol on HPAC function is appropriate here as background. Ellis was the first to show progressive adrenocortical activation as measured directly by plasma corticosterone levels with increasing doses of alcohol given intraperitoneally to rats.5 At the lowest dose given (0.5 mg/kg body weight), he reported no “perceptible” depression of the CNS but found a minimal increase in plasma corticosterone levels. These data suggested, at least in rats, that pituitary adrenocortical activation could occur after alcohol without detectable behavioral changes. Recently, experiments on anesthetized animals have helped separate the effect of pain from the alcohol injection or alcohol-induced behavioral change from the direct effect of alcohol on activating the pituitary adrenocortical system. Thus, Ellis, in a series of revealing experiment^,^ confirmed the findings of Czaja and Kalant,2 who presented some similar data showing no inhibition of the corticosterone response to alcohol in rats pretreated with local anesthetic intraperitoneally. Pentobarbital in large doses had been shown to inhibit the HPAC response to s t r e s ~ . ~ Ellis demonstrated that pentobarbital anesthesia in rats (50 mg/kg) reduced the corticosterone response to alcohol (2 mg/kg) given about ten minutes after anesthesia to approximately 50% of the response seen in nonanesthetized animals. These are important data in that they are the first to support the hypothesis that alcohol per se induces adrenal activation without detectable behavioral alteration as a necessary precursor. Morphine has been shown to have a blocking action on the HPAC system, and