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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Behavioral Neuroscience Department and Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Raúl
authors.initials: R
authors.lastname: Pastor
authors.forename: Cheryl
authors.initials: C
authors.lastname: Reed
authors.forename: Sue
authors.initials: S
authors.lastname: Burkhart-Kasch
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Sharpe
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Coste
authors.forename: Mary P
authors.initials: MP
authors.lastname: Stenzel-Poore
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Phillips
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011803:Quinine / Q000008:administration & dosage; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012439:Saccharin / Q000008:administration & dosage; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics; D013550:Swimming; D013995:Time; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D011803:Quinine; D012439:Saccharin