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Updated: May 21, 2026
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Modeling Alcohol Consumption in Rodents Using Two-Bottle Choice Home Cage Drinking and Microstructural Analysis
Published on: November 8, 2024
Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.
Leandro F Vendruscolo1, Estelle Barbier, Joel E Schlosburg
1Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Summary
Glucocorticoid receptor (GR) system alterations drive alcohol dependence. Blocking GR with mifepristone reduced compulsive alcohol drinking and may offer a new alcoholism treatment target.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Alcoholism involves compulsive alcohol seeking and intake, with negative emotional states during abstinence.
- Neuroendocrine stress system activation, particularly the hypothalamic-pituitary-adrenal axis, is implicated in alcohol dependence.
- Alterations in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation may drive compulsive alcohol consumption.
Purpose of the Study:
- To investigate the role of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in alcohol dependence.
- To determine if GR antagonism can prevent or reverse alcohol-induced compulsive drinking.
Main Methods:
- Rats were exposed to alcohol vapor to induce dependence.
- Compulsive drinking was assessed using progressive-ratio responding and punishment paradigms (quinine addition).
- Messenger RNA (mRNA) levels of GR and MR in brain regions were analyzed. GR antagonism was achieved using mifepristone (RU38486).
Main Results:
- Dependence increased alcohol intake and compulsive drinking, persisting despite punishment.
- Acute withdrawal downregulated GR mRNA in stress/reward areas; protracted abstinence upregulated it in specific regions (NAc core, ventral BNST, central amygdala).
- Mifepristone treatment prevented alcohol intake escalation and compulsive responding during both chronic exposure and protracted abstinence.
Conclusions:
- The GR system is significantly involved in the development of alcohol dependence.
- GR antagonism effectively blocks escalated alcohol drinking and compulsive behaviors associated with alcohol dependence.
- The GR system represents a promising pharmacological target for treating alcoholism.
