title: CRF1 receptor signaling regulates food and fluid intake in the drinking-in-the-dark model of binge alcohol consumption.
abstract: BACKGROUND
  Several recent studies implementing the standard "drinking-in-the-dark" (DID) model of short-term binge-like ethanol (EtOH) intake in C57BL/6J mice highlighted a role for the stress-related neuropeptide corticotropin-releasing factor (CRF) and its primary binding partner, the CRF type-1 (CRF1) receptor.
  
  
  METHODS
  We evaluated the selectivity of CRF1 involvement in binge-like EtOH intake by interrupting CRF1 function via pharmacological and genetic methods in a slightly modified 2-bottle choice DID model that allowed calculation of an EtOH preference ratio. In addition to determining EtOH intake and preference, we also measured consumption of food and H2 O during the DID period, both in the presence and absence of EtOH and sweet tastant solutions.
  
  
  RESULTS
  Treatment with either of the CRF1-selective antagonists CP-376,395 (CP; 10 to 20 mg/kg, i.p.) or NBI-27914 (10 to 30 mg/kg, i.p.) decreased intake of 15% EtOH in male C57BL/6J mice, but did so in the absence of a concomitant decrease in EtOH preference. These findings were replicated genetically in a CRF1 knockout (KO) mouse model (also on a C57BL/6J background). In contrast to effects on EtOH intake, pharmacological blockade of CRF1 with CP increased intake of 10% sucrose, consistent with previous findings in CRF1 KO mice. Finally, pharmacological and genetic disruption of CRF1 activity significantly reduced feeding and/or total caloric intake in all experiments, confirming the existence of nonspecific effects.
  
  
  CONCLUSIONS
  Our findings indicate that blockade of CRF1 receptors does not exert specific effects on EtOH intake in the DID paradigm, and that slight modifications to this procedure, as well as additional consummatory control experiments, may be useful when evaluating the selectivity of pharmacological and genetic manipulations on binge-like EtOH intake.
authors: Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR 97239, USA.
authors: William J
authors: WJ
authors: Giardino
authors: Andrey E
authors: AE
authors: Ryabinin
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D063425:Binge Drinking / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D003624:Darkness; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011743:Pyrimidines / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: C529296:(3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine; C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000631:Aminopyridines; D000814:Aniline Compounds; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1
keywords: Alcohol; Binge; Corticotropin; Stress; Urocortin
references: Neuroscience. 2012 Mar 29;206:155-66
references: 22245501
references: Neuropsychopharmacology. 2010 May;35(6):1241-52
references: 20130533
references: Peptides. 2000 May;21(5):669-77
references: 10876049
references: Endocrinology. 2000 Jul;141(7):2698-702
references: 10875276
references: Genes Brain Behav. 2007 Feb;6(1):1-18
references: 17233637
references: Front Neuroendocrinol. 2007 Apr;28(1):1-27
references: 17083971
references: Alcohol. 2012 Jun;46(4):349-57
references: 22444954
references: J Pharmacol Exp Ther. 2003 Apr;305(1):385-93
references: 12649393
references: Psychopharmacology (Berl). 2012 Feb;219(4):1055-63
references: 21833501
references: Birth Defects Res A Clin Mol Teratol. 2012 Aug;94(8):570-5
references: 22706886
references: J Neurosci. 2012 Mar 7;32(10):3405-13
references: 22399763
references: J Pharmacol Exp Ther. 2000 Jun;293(3):799-806
references: 10869378
references: Alcohol Clin Exp Res. 2010 Sep 1;34(9):1525-34
references: 20586761
references: Alcohol Clin Exp Res. 2008 Nov;32(11):1962-8
references: 18782340
references: Psychopharmacology (Berl). 2003 Jan;165(3):296-305
references: 12442202
references: Alcohol Clin Exp Res. 2005 Aug;29(8):1419-26
references: 16131849
references: Endocrinology. 2000 Aug;141(8):2715-24
references: 10919255
references: Neth J Med. 2008 Dec;66(11):467-73
references: 19075312
references: Brain Res. 2009 Oct 13;1293:61-75
references: 19332030
references: Physiol Behav. 2005 Jan 31;84(1):53-63
references: 15642607
references: Nat Rev Neurosci. 2011 Oct 20;12(11):670-84
references: 22011682
references: PLoS One. 2011;6(10):e26997
references: 22046429
references: Neuron. 2008 Jul 10;59(1):11-34
references: 18614026
references: Neuron. 2012 Oct 4;76(1):192-208
references: 23040815
references: J Neurosci. 2008 Jan 9;28(2):407-14
references: 18184783
references: Nat Rev Neurosci. 2011 Dec 20;13(1):70; author reply 70
references: 22183439
references: CNS Neurol Disord Drug Targets. 2010 Mar;9(1):77-86
references: 20201818
references: Psychopharmacology (Berl). 2006 Dec;189(2):175-86
references: 17047935
references: Genes Brain Behav. 2011 Feb;10(1):78-89
references: 20731720
references: Front Neuroanat. 2012 Feb 14;6:5
references: 22347848
references: Science. 1996 Sep 13;273(5281):1561-4
references: 8703220
references: Science. 2002 May 3;296(5569):931-3
references: 11988580
references: Alcohol Clin Exp Res. 2008 Feb;32(2):259-65
references: 18162072
references: Psychol Bull. 2009 Jan;135(1):142-56
references: 19210057
references: Pharmacol Biochem Behav. 1983 Nov;19(5):771-5
references: 6359178
references: Acta Neurol Taiwan. 2012 Mar;21(1):39-43
references: 22879089
references: J Clin Psychiatry. 2006 Jul;67(7):e02
references: 17107227
references: Alcohol Clin Exp Res. 2012 Feb;36(2):369-76
references: 21895713
references: Neuropsychopharmacology. 2012 Mar;37(4):1047-56
references: 22113086
references: Peptides. 1985;6 Suppl 3:53-7
references: 3879535
references: Ann N Y Acad Sci. 2011 Jan;1216:24-40
references: 21272009
references: Brain Res Rev. 2006 Sep;52(2):368-80
references: 16766036
references: Neuroreport. 1998 May 11;9(7):1601-6
references: 9631473
references: Brain Res. 2010 Feb 16;1314:3-14
references: 19912996
references: Trends Neurosci. 2007 Aug;30(8):399-406
references: 17629579
references: Nat Genet. 1998 Jun;19(2):162-6
references: 9620773
references: Neuroscience. 2008 Feb 6;151(3):780-90
references: 18164138