Glucocorticoid receptor modulators decrease alcohol self-administration in male rats

被引：20

作者：

McGinn, M. Adrienne ^{[1
]}

Tunstall, Brendan J. ^{[2
]}

Schlosburg, Joel E. ^{[3
]}

Gregory-Flores, Adriana ^{[4
]}

George, Olivier ^{[5
]}

de Guglielmo, Giordano ^{[5
]}

Mason, Barbara J. ^{[6
,7
]}

Hunt, Hazel J. ^{[8
]}

Koob, George F. ^{[1
]}

Vendruscolo, Leandro F. ^{[1
]}

机构：

[1] NIDA, Integrat Neurosci Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[2] Univ Tennessee, Dept Pharmacol Addict Sci & Toxicol, Hlth Sci Ctr, Knoxville, TN 37996 USA

[3] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA

[4] Univ Texas Austin, Inst Neurosci, Austin, TX 78712 USA

[5] Univ Calif San Diego, Sch Med, Dept Psychiat, 9500 Gillman Dr, La Jolla, CA 92093 USA

[6] Scripps Res Inst, Dept Mol Med, La Jolla, CA USA

[7] Scripps Res Inst, Pearson Ctr Alcoholism & Addict Res, La Jolla, CA USA

[8] Corcept Therapeut, Menlo Pk, CA USA

来源：

NEUROPHARMACOLOGY | 2021年 / 188卷

关键词：

Alcohol dependence; Alcohol drinking; Addiction; Alcoholism; ETHANOL-CONSUMPTION; CENTRAL NUCLEUS; STRESS; BRAIN; MIFEPRISTONE; ANTAGONIST; DRINKING; DEPENDENCE; CORTICOSTERONE; WITHDRAWAL;

D O I：

10.1016/j.neuropharm.2021.108510

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alcohol use disorder (AUD) is associated with the dysregulation of brain stress and reward systems, including glucocorticoid receptors (GRs). The mixed glucocorticoid/progesterone receptor antagonist mifepristone and selective GR antagonist CORT113176 have been shown to selectively reduce alcohol consumption in alcoholdependent rats. Mifepristone has also been shown to decrease alcohol consumption and craving for alcohol in humans with AUD. The present study tested the effects of the GR modulators CORT118335, CORT122928, CORT108297, and CORT125134 on alcohol self-administration in nondependent (air-exposed) and alcoholdependent (alcohol vapor-exposed) adult male rats. Different GR modulators recruit different GR-associated transcriptional cofactors. Thus, we hypothesized that these GR modulators would vary in their effects on alcohol drinking. CORT118335, CORT122928, and CORT125134 significantly reduced alcohol selfadministration in both alcohol-dependent and nondependent rats. CORT108297 had no effect on alcohol selfadministration in either group. The present results support the potential of GR modulators for the development of treatments for AUD. Future studies that characterize genomic and nongenomic effects of these GR modulators will elucidate potential molecular mechanisms that underlie alcohol drinking in alcohol-dependent and nondependent states.

引用

页数：7

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