Mice deficient in corticotropin-releasing factor receptor type 2 exhibit normal ethanol-associated behaviors

Background: Stress is believed to influence alcohol use and relapse in alcoholics. Animal studies suggest an interaction between corticotropin- releasing factor (CRF) and its receptors and the behavioral effects and consumption of alcohol. The objective of these studies was to examine the effect of corticotropin-releasing factor receptor type 2 (CRF₂) on ethanol consumption, conditioned taste aversion, sedation, and hypothermia. Methods: CRF₂-null mutant or knock-out (KO), and wild-type (WT) mice were used to assess consumption of increasing concentrations of ethanol in a two-bottle, 24-hr test and during daily limited-access sessions. Ethanol-induced conditioned taste aversion (CTA), loss of righting reflex (LORR), hypothermia, and ethanol metabolism kinetics were also examined in the CRF₂ KO and WT mice. Results: CRF₂ KO mice did not differ from WT mice in sensitivity to ethanol-induced CTA, LORR, hypothermia, or ethanol metabolism kinetics. There was no genotypic difference in ethanol intake or preference in the 24-hr, two-bottle choice procedure, and only modestly reduced consumption of the 7.5 and 10% ethanol solutions in KO versus WT mice in the limited-access procedure. Conclusions: CRF₂ deficiency had little effect on several ethanol-associated behaviors in CRF₂-null mutant compared with WT mice, suggesting that this receptor does not have a primary role in modulating these behaviors. Evidence of a role for this receptor in neural circuits subserving stress-coping behaviors suggest that future studies should focus on the role of endogenous CRF₂ in ethanol-associated behaviors in mice that are stressed or withdrawing from dependence on ethanol.