Learned tolerance to the corticosterone-increasing action of ethanol in rats.

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.