Persistent Escalation of Alcohol Consumption by Mice Exposed to Brief Episodes of Social Defeat Stress: Suppression by CRF-R1 Antagonism

The study investigated the impact of social defeat stress on alcohol consumption in male C57BL/6J mice and tested various drugs targeting the HPA axis and extrahypothalamic neural substrates. Socially defeated mice exhibited increased alcohol intake compared to controls, with intermittent access leading to higher consumption than continuous access. The CRF-R1 antagonist CP376395 reduced alcohol intake in mice with continuous access but not intermittent access. Mifepristone increased drinking in intermittently-accessed mice while reducing it in continuously-accessed mice. Both finasteride and metyrapone reduced alcohol intake across all mice. The findings suggested that CRF-R1 antagonism could be a potential treatment for alcohol use disorders in individuals experiencing repeated psychosocial stress.