A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice.

Abstract

Corticotropin-releasing factor (CRF) plays an integral role in mediating stress responses and anxiety. However, little is known regarding the role of CRF in ethanol consumption, a behavior often associated with stress and anxiety in humans. The present study sought to determine the role of CRF in ethanol consumption, locomotor sensitivity and reward by examining these behaviors in C57BL/6J x 129S mice with a targeted disruption in the gene encoding the CRF prohormone. Male wild-type and CRF-deficient mice were given concurrent access to ethanol and water in both limited and unlimited-access two-bottle choice paradigms. Taste reactivity (saccharin or quinine vs water) was examined in a similar manner under continuous-access conditions. Blood ethanol levels and clearance were measured following limited ethanol access as well as a 4-g/kg i.p. injection of ethanol. Locomotor stimulant effects of ethanol were measured in an open-field testing chamber, and the rewarding effects of ethanol were examined using the conditioned place preference paradigm. CRF-deficient mice displayed normal body weight, total fluid intake, taste reactivity and blood ethanol clearance, but consumed approximately twice as much ethanol as wild types in both continuous- and limited-access paradigms. CRF-deficient mice failed to demonstrate a locomotor stimulant effect following acute administration of ethanol (2 g/kg i.p.), and also failed to demonstrate a conditioned place preference to ethanol at 2 g/kg i.p., but did display such a preference at 3 g/kg i.p. CRF deficiency may lead to excessive ethanol consumption by reducing sensitivity to the locomotor stimulant and rewarding effects of ethanol.