CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Binge-like ethanol consumption is a significant public health concern.
• Corticotropin-releasing factor receptor (CRFR) signaling is implicated in alcohol intake.
• Further characterization of CRFR signaling's role in binge drinking is needed.

Purpose of the Study:

• To investigate the role of central CRFR signaling in modulating binge-like ethanol consumption in C57BL/6J mice.
• To assess the contribution of CRF type 1 receptor (CRF1R) and CRF type 2 receptor (CRF2R) signaling.
• To determine the involvement of the hypothalamic-pituitary-adrenal (HPA) axis.

Main Methods:

• Intracerebroventricular (i.c.v.) infusion of CRFR antagonist alpha-helical CRF(9-41) and CRF(2)R agonist urocortin 3.
• Intraperitoneal (i.p.) administration of metyrapone and mifepristone to assess HPA axis involvement.
• Assessment of CP-154,526 efficacy in adrenalectomized (ADX) and normal mice.

Main Results:

• Central CRFR blockade and CRF(2)R activation significantly attenuated binge-like ethanol consumption.
• CRF(1)R antagonist CP-154,526 reduced ethanol intake in both ADX and normal mice.
• HPA axis manipulation (metyrapone, mifepristone) did not selectively alter ethanol consumption.

Conclusions:

• CRF(1)R and CRF(2)R signaling pathways modulate binge-like ethanol intake in mice.
• CRF(1)R blockade or CRF(2)R activation can effectively reduce excessive alcohol consumption.
• Normal HPA axis signaling is not essential for binge-like drinking behavior.