title: Corticotropin-releasing factor acting on corticotropin-releasing factor receptor type 1 is critical for binge alcohol drinking in mice.
abstract: BACKGROUND
  The corticotropin-releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access "drinking in the dark" (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild-type (WT) littermates using the DID paradigm.
  
  
  METHODS
  On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20% ethanol or 10% sucrose for 2 hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4 hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis.
  
  
  RESULTS
  CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs.
  
  
  CONCLUSIONS
  Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.
authors: Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors: Simranjit
authors: S
authors: Kaur
authors: Ju
authors: J
authors: Li
authors: Mary P
authors: MP
authors: Stenzel-Poore
authors: Andrey E
authors: AE
authors: Ryabinin
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D000431:Ethanol / Q000097:blood; D005260:Female; D017353:Gene Deletion; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013395:Sucrose; D054832:Urocortins / Q000235:genetics; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D002492:Central Nervous System Depressants; D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000431:Ethanol; D013395:Sucrose; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone