Ethanol concentration-dependent effects and the role of stress on ethanol drinking in corticotropin-releasing factor type 1 and double type 1 and 2 receptor knockout mice

Rationale Exposure to stressors promotes ethanol (EtOH) consumption and enhances drug craving during abstinence. Corticotropin-releasing factor (CRF), and in particular, CRF actions via type 1 CRF receptors (CRF ₁) are critical in behavioral responses to stressors. CRF ₁ play a role in EtOH-induced behavioral neuroadaptation, in binge-like EtOH consumption, and in heightened EtOH consumption in dependent animals. Objectives We investigated the involvement of CRF ₁ in swim-stress-induced changes in EtOH consumption and in baseline consumption as a function of EtOH concentration. The role of CRF ₂ in adapting to effects of the stressor was also examined. Methods Wild-type mice and knockout mice lacking CRF ₁ were tested for two-bottle choice EtOH consumption at concentrations of 3-20%. Also, intake of 10% EtOH was examined in wild-type mice and knockout mice lacking CRF ₁, or lacking both CRF ₁ and CRF ₂, before and after acute or repeated swim stress exposures. Results EtOH intake was reduced in CRF ₁ compared with wild-type mice when presented at a concentration of 20% but not when presented at lower concentrations. No genotype-dependent effects were found for saccharin or quinine drinking. Acute swim stress had no effect, but repeated swim stress resulted in higher levels of EtOH consumption in wild-type mice, compared with both types of knockout mice. Stress effects on EtOH drinking were longer lasting in double knockout mice. Conclusions These data suggest a prominent role of CRF ₁ in stressor-induced changes in EtOH consumption, with involvement of CRF ₂ in recovery from stressor effects.