Cortexolone antagonizes development of alcohol tolerance in mice

Area of Science:

• Neuropharmacology
• Endocrinology

Background:

• Chronic ethanol consumption leads to the development of tolerance.
• The mechanisms underlying alcohol tolerance are not fully understood.
• Glucocorticoid receptors are involved in various physiological processes, including stress response and neuroadaptation.

Purpose of the Study:

• To investigate the role of the glucocorticoid receptor in the development of ethanol tolerance.
• To determine if cortexolone, a glucocorticoid receptor blocker, affects ethanol tolerance.

Main Methods:

• Mice were subjected to chronic ethanol feeding.
• Cortexolone or vehicle was administered daily to ethanol-fed mice.
• Ethanol challenge doses were administered to assess tolerance.
• Hypnotic effects of ethanol were measured in naive mice.
• Ethanol consumption and blood ethanol levels were monitored.

Main Results:

• Mice treated with cortexolone during chronic ethanol feeding showed significantly less tolerance to ethanol.
• Cortexolone did not alter the acute hypnotic effects of ethanol in naive mice.
• Ethanol consumption and blood ethanol levels were not affected by cortexolone treatment.

Conclusions:

• Cortexolone interferes with the development of tolerance to ethanol.
• These findings suggest that the glucocorticoid receptor system plays a role in mediating alcohol tolerance.
• Targeting the glucocorticoid receptor may represent a novel therapeutic strategy for alcohol use disorder.