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 rep eated administration such that plasma corticosterone levels become les s effected by subsequent ethanol administration. The present experimen t 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 r eceived intragastric administrations of ethanol (3.2 g/kg) in associat ion with one set of environmental cues and intragastric saline in asso ciation with a different set of environmental cues. Plasma corticoster one levels were elevated after the first ethanol administration, but a fter the tenth ethanol administration, corticosterone levels failed to increase significantly above control values. After demonstrating tole rance, rats were administered ethanol in the saline-paired environment and plasma corticosterone levels were higher than in the ethanol-pair ed 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 effect s of ethanol. Copyright (C) 1996 Elsevier Science Inc.