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

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.

Mifepristone in the Central Nucleus of the Amygdala Reduces Yohimbine Stress-Induced Reinstatement of Ethanol-Seeking

“…In agreement with this analysis, it has been shown that while mifepristone has no effect on baseline drinking in mice, it blocks stress-induced increases in drinking caused by daily vehicle injections (O'Callaghan et al, 2005). In conditions where stress is limited, mifepristone has no effect on ethanol intake (Fahlke et al, 1994(Fahlke et al, , 1995(Fahlke et al, , 1996Lowery et al, 2010;Yang et al, 2008).…”

“…The anti-GC activity of mifepristone has made it a potential treatment for Cushing's syndrome (Johanssen and Allolio, 2007) and neurological and psychological disorders (DeBattista and Belanoff, 2006;Gallagher and Young, 2006;Gallagher et al, 2005Gallagher et al, , 2008Wulsin et al, 2010;Young, 2006). The drug has also been examined in the self-administration of amphetamine (De Vries et al, 1996), cocaine (Deroche-Gamonet et al, 2003;Fiancette et al, 2010), morphine (Mesripour et al, 2008), and ethanol, where it has been shown to have either no effect or decrease baseline ethanol consumption (Fahlke et al, 1995;Jacquot et al, 2008;Koenig and Olive, 2004;Lowery et al, 2010;O'Callaghan et al, 2005;Roberts et al, 1995;Yang et al, 2008). However, the role of mifepristone in stress-induced reinstatement of ethanol-seeking is not known.…”

“…The literature is somewhat mixed when examining the effects of mifepristone on ethanol consumption as some authors have reported decreases in consumption following drug treatment (Koenig and Olive, 2004;O'Callaghan et al, 2005), while others have reported no change (Fahlke et al, 1994(Fahlke et al, , 1995(Fahlke et al, , 1996Lowery et al, 2010;Yang et al, 2008). Koenig and Olive (2004) demonstrated significant decreases in consumption using a limited-access, two-bottle-choice paradigm; however, it is important to note that the animals were fluid restricted for 23 h a day (O'Callaghan et al, 2005).…”

An Initial, Three-Day-Long Treatment with Alcohol Induces a Long-Lasting Phenomenon of Selective Tolerance in the Activity of the Rat Hypothalamic–Pituitary–Adrenal Axis

“…It is therefore obvious that this drug, particularly if it is administered repeatedly, will threaten homeostasis via a variety of mechanisms. In addition, an emerging hypothesis is that hormones of the HPA axis can promote drug use (Cador et al, 1992;Deroche et al, 1993;Piazza et al, 1993;Fahlke et al, 1995;Lamblin and De Witte, 1996;Shaham et al, 1996). Consequently, sensitization to alcohol may reinforce its consumption, whereas, conversely, animals rendered tolerant may attempt to restore normal concentrations of ACTH, corticosterone, and CRF by consuming everincreasing doses of the drug.…”

Response of the Hypothalamic-Pituitary-Adrenal Axis to Stress in the Absence and Presence of Ethanol in Subjects at High and Low Risk of Alcoholism,

“…CRH stimulates cells of the anterior pituitary to synthesize and release ACTH, which in turn stimulates the synthesis and release of cortisol by the adrenal cortex. Furthermore, both CRH and cortisol have been reported to influence drinking behavior (Fahlke et al 1995;Koob and Britton 1996;Erb et al 1998;Le et al 1998). Accepting that components of the HPA-axis can modulate alcohol consumption, then genetic or environmental factors that influence the activity of the HPA-axis may be important in determining a person's drinking behavior.…”