Glucocorticoid receptor modulators decrease alcohol self-administration in male rats
| Autor: | Brendan J. Tunstall, Adriana Gregory-Flores, George F. Koob, Olivier George, Joel E. Schlosburg, Giordano de Guglielmo, Leandro F. Vendruscolo, M. Adrienne McGinn, Hazel Hunt, Barbara J. Mason |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Pyridines Wistar Alcohol Craving Self Administration Alcohol drinking Alcohol use disorder Cardiovascular Oral and gastrointestinal chemistry.chemical_compound Alcohol Use and Health Substance Misuse 0302 clinical medicine Glucocorticoid receptor Glucocorticoid Heterocyclic Compounds Receptors Medicine Psychology Cancer Substance Abuse Alcohol dependence Mifepristone Pharmacology and Pharmaceutical Sciences Stroke Alcoholism Mental health medicine.symptom medicine.drug medicine.medical_specialty 1.1 Normal biological development and functioning Addiction Heterocyclic Compounds 4 or More Rings Basic Behavioral and Social Science Article 03 medical and health sciences Cellular and Molecular Neuroscience Receptors Glucocorticoid Underpinning research Internal medicine Progesterone receptor Behavioral and Social Science Animals Rats Wistar Pharmacology Aza Compounds Neurology & Neurosurgery Ethanol business.industry Neurosciences 4 or More Rings medicine.disease Isoquinolines Rats Brain Disorders 030104 developmental biology Endocrinology Good Health and Well Being chemistry Pyrazoles business 030217 neurology & neurosurgery Thymine |
| Zdroj: | Neuropharmacology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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