The hypothalamopituitary-adrenal axis and alcohol preference

Area of Science:

• Neuroendocrinology
• Behavioral Pharmacology

Background:

• Stress hormones, particularly glucocorticoids, are implicated in the development and maintenance of alcohol use disorders.
• Understanding the specific roles of different glucocorticoid receptor types and their signaling pathways is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the effects of modulating stress hormone pathways on alcohol preference in mice.
• To determine the involvement of Type I and Type II glucocorticoid receptors and the corticotropin-releasing factor (CRF) system in alcohol consumption.

Main Methods:

• Administration of various pharmacological agents including RU38486 (Type II glucocorticoid receptor antagonist), spironolactone (Type I antagonist), metyrapone (corticosterone synthesis inhibitor), corticosterone, ACTH, CRF, and a CRF antagonist (alpha-helical CRF9-41) via intraperitoneal or intracerebroventricular routes.
• Assessment of alcohol consumption in mice with high and low alcohol preference following drug administration.
• Measurement of blood corticosterone concentrations.

Main Results:

• Repeated administration of RU38486 prevented an increase in alcohol consumption in low-preference mice previously exposed to vehicle injections.
• Repeated administration of metyrapone reduced alcohol preference in both high and low-preference mice and prevented stress-induced increases in consumption.
• CRF administration did not alter alcohol preference, but the CRF antagonist caused a transient increase in preference in low-preference mice.

Conclusions:

• Delayed effects of corticosterone acting on Type II glucocorticoid receptors may contribute to increased alcohol preference following stress.
• Central CRF signaling may play a role in maintaining low alcohol consumption in susceptible individuals.