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
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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 (CRF1) are critical in behavioral responses to stressors. CRF1 play a role in EtOH-induced behavioral neuroadaptation, in binge-like EtOH consumption, and in heightened EtOH consumption in dependent animals.
We investigated the involvement of CRF1 in swim-stress-induced changes in EtOH consumption and in baseline consumption as a function of EtOH concentration. The role of CRF2 in adapting to effects of the stressor was also examined.
Wild-type mice and knockout mice lacking CRF1 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 CRF1, or lacking both CRF1 and CRF2, before and after acute or repeated swim stress exposures.
EtOH intake was reduced in CRF1 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.
These data suggest a prominent role of CRF1 in stressor-induced changes in EtOH consumption, with involvement of CRF2 in recovery from stressor effects.
KeywordsCRF Stress Knockout Alcohol Drinking Swim stress
This work was supported by a grant from the Department of Veterans Affairs and NIH grants from the National Institute of Alcohol Abuse and Alcoholism (R01AA13331 and P60AA010760) and from Mental Health (R01MH65689).
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