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Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat,and the effect of type I and type II corticosteroid receptor antagonists
Authors:C Fahlke  E Hård  S Hansen  C J P Eriksson  J A Engel
Institution:(1) Department of Psychology, Göteborg University, P.O. Box 14158, S-40020 Göteborg, Sweden;(2) Biomedical Research Center, Alko Ltd., FIN-00100 Helsinki, Finland;(3) Department of Pharmacology, Göteborg University, S-40033 Göteborg, Sweden
Abstract:The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.
Keywords:Alcohol drinking  Adrenalectomy  Corticosterone  Dexamethasone  Drug abuse  Mifepristone  RU 28318  RU 38486
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