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 increased [corrected] 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.
Sharpe
Amanda L
AL
Department of Behavioral Neuroscience, the Portland Alcohol Research Center, Oregon Health & Science University, and the Research Service, Portland VA Medical Center, Portland, Oregon 97239, USA. sharpea@ohsu.edu
Coste
Sarah C
SC
Burkhart-Kasch
Sue
S
Li
Na
N
Stenzel-Poore
Mary P
MP
Phillips
Tamara J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D013649:Taste
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone