Seeley R J, Hawkins M H, Ramsay D S, Wilkinson C W, Woods S C
Department of Psychology, University of Washington, Seattle, USA.
Pharmacol Biochem Behav. 1996 Oct;55(2):268-73. doi: 10.1016/s0091-3057(96)00081-0.
Ethanol administration stimulates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased plasma levels of corticosterone. As occurs with many other effects of ethanol, tolerance develops with repeated administration such that plasma corticosterone levels become less effected by subsequent ethanol administration. The present experiment explored the possibility that the environmental cues associated with the administration of ethanol can control the expression of tolerance to ethanol's corticosterone-elevating effects. Male Long-Evans rats received intragastric administrations of ethanol (3.2 g/ kg) in association with one set of environmental cues and intragastric saline in association with a different set of environmental cues. Plasma corticosterone levels were elevated after the first ethanol administration, but after the tenth ethanol administration, corticosterone levels failed to increase significantly above control values. After demonstrating tolerance, rats were administered ethanol in the saline-paired environment and plasma corticosterone levels were higher than in the ethanol-paired environment. This environmental specificity suggests that tolerance to the neuroendocrine effects of ethanol is not simply the result of long-term alterations in sensitivity of the HPA axis but is, at least in part, mediated by learned responses to cues that predict the effects of ethanol.
给予乙醇会刺激下丘脑 - 垂体 - 肾上腺（HPA）轴，导致血浆皮质酮水平升高。正如乙醇的许多其他效应一样，反复给药会产生耐受性，使得后续给予乙醇时血浆皮质酮水平受到的影响变小。本实验探讨了与乙醇给药相关的环境线索能否控制对乙醇升高皮质酮效应的耐受性表达。雄性Long-Evans大鼠在一组环境线索下接受胃内给予乙醇（3.2克/千克），在另一组不同的环境线索下接受胃内给予生理盐水。首次给予乙醇后血浆皮质酮水平升高，但在第十次给予乙醇后，皮质酮水平未能显著高于对照值而增加。在证明产生耐受性后，在与生理盐水配对的环境中给大鼠给予乙醇，此时血浆皮质酮水平高于与乙醇配对的环境。这种环境特异性表明，对乙醇神经内分泌效应的耐受性不仅仅是HPA轴敏感性长期改变的结果，至少部分是由对预测乙醇效应的线索的习得反应介导的。
