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Related Experiment Video

Updated: Nov 15, 2025

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Glucocorticoid receptor modulators decrease alcohol self-administration in male rats.

M Adrienne McGinn1, Brendan J Tunstall2, Joel E Schlosburg3

  • 1Integrative Neuroscience Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.

Neuropharmacology
|March 1, 2021
PubMed
Summary

Glucocorticoid receptor (GR) modulators like CORT118335, CORT122928, and CORT125134 effectively reduced alcohol self-administration in both dependent and nondependent rats, suggesting potential for alcohol use disorder treatments.

Keywords:
AddictionAlcohol dependenceAlcohol drinkingAlcoholism

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Alcohol use disorder (AUD) involves dysregulation of brain stress and reward systems, particularly glucocorticoid receptors (GRs).
  • Previous studies show mifepristone and CORT113176 reduce alcohol consumption in rats and humans with AUD.

Purpose of the Study:

  • To investigate the effects of novel GR modulators (CORT118335, CORT122928, CORT108297, CORT125134) on alcohol self-administration in rats.
  • To determine if different GR modulators have varying impacts on alcohol consumption based on their cofactor recruitment.

Main Methods:

  • Adult male rats were exposed to alcohol vapor (dependent) or air (nondependent).
  • Rats self-administered alcohol following administration of different GR modulators.
  • Alcohol consumption was measured to assess the efficacy of each compound.

Main Results:

  • CORT118335, CORT122928, and CORT125134 significantly decreased alcohol self-administration in both alcohol-dependent and nondependent rats.
  • CORT108297 did not affect alcohol self-administration in either group.
  • The results indicate differential effects of GR modulators on alcohol consumption.

Conclusions:

  • GR modulators CORT118335, CORT122928, and CORT125134 show promise as potential therapeutic agents for AUD.
  • Further research into the molecular mechanisms of these GR modulators is warranted to understand their effects on alcohol drinking.