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Neuropharmacology
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Neuropharmacology
Article . 2021 . Peer-reviewed
License: Elsevier TDM
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Glucocorticoid receptor modulators decrease alcohol self-administration in male rats

Authors: M. Adrienne McGinn; Brendan J. Tunstall; Joel E. Schlosburg; Adriana Gregory-Flores; Olivier George; Giordano de Guglielmo; Barbara J. Mason; +3 Authors

Glucocorticoid receptor modulators decrease alcohol self-administration in male rats

Abstract

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 alcohol-dependent 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 alcohol-dependent (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 self-administration in both alcohol-dependent and nondependent rats. CORT108297 had no effect on alcohol self-administration 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.

Country
United States
Keywords

Male, Pyridines, Biological Psychology, 150, Wistar, Alcohol drinking, Self Administration, Cardiovascular, Oral and gastrointestinal, Substance Misuse, Alcohol Use and Health, Glucocorticoid, Heterocyclic Compounds, Receptors, Psychology, Cancer, 600, Alcohol dependence, Pharmacology and Pharmaceutical Sciences, Stroke, Alcoholism, Mifepristone, 5.1 Pharmaceuticals, Mental health, 1.1 Normal biological development and functioning, 610, Addiction, Basic Behavioral and Social Science, Heterocyclic Compounds, 4 or More Rings, Receptors, Glucocorticoid, Underpinning research, Behavioral and Social Science, Animals, Rats, Wistar, Aza Compounds, Neurology & Neurosurgery, Biomedical and Clinical Sciences, Ethanol, Neurosciences, 4 or More Rings, Isoquinolines, Brain Disorders, Rats, Good Health and Well Being, Pharmacology and pharmaceutical sciences, Biological psychology, Pyrazoles, Thymine

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