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  • Title: 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.
    Author: Pastor R, Reed C, Burkhart-Kasch S, Li N, Sharpe AL, Coste SC, Stenzel-Poore MP, Phillips TJ.
    Journal: Psychopharmacology (Berl); 2011 Nov; 218(1):169-77. PubMed ID: 21487655.
    Abstract:
    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.
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