title: Reduction of ethanol intake by corticotropin-releasing factor receptor-1 antagonist in "heavy-drinking" mice in a free-choice paradigm.
abstract: BACKGROUND
  We hypothesized that the corticotropin-releasing factor (CRF) system is hyperresponsive in animals with high ethanol intake, which exhibits a reduction of ethanol intake when administered with a CRF1 receptor antagonist.
  
  
  METHODS
  Outbred Swiss mice were subjected to a long-term, three-bottle, free-choice paradigm (5 and 10 % [v/v] ethanol and water) that consisted of four phases: acquisition (AC; 10 weeks), withdrawal (W; 2 weeks), reexposure (RE; 2 weeks), and quinine-adulteration (AD; 2 weeks). Based on individual ethanol intake, the mice were classified into three groups: A group, preference for ethanol and persistently high consumption during AD phase; B group, preference for ethanol and a reduction of ethanol intake in the AD phase; and C group; preference for water during all phases. A control group only had access to water. CRF1 receptor messenger RNA (mRNA) levels in the amygdala and the effect of the CRF1 receptor antagonist CP-154,526 on ethanol and water intake in the subgroups were studied.
  
  
  RESULTS
  CRF1 transcript levels were higher in the B group than in the control group. The highest dose of CP-154,526 reduced ethanol intake and preference, with no changes in water consumption, in the A group compared with vehicle. The B group exhibited a reduction of both ethanol and water intake, with no changes in preference. The C group exhibited no changes in response to the CRF1 antagonist.
  
  
  CONCLUSIONS
  CRF1 receptors appear to be involved in ethanol consumption in mice with high ethanol consumption, and CRF system-mediated neuroadaptations depend on drinking profiles.
authors: Departamento de Farmacologia, Jardim das Américas, Universidade Federal do Paraná, P.O. Box 19031, Curitiba, PR, 81531-990, Brazil.
authors: Diego
authors: D
authors: Correia
authors: Bruno Jacson
authors: BJ
authors: Martynhak
authors: Marcela
authors: M
authors: Pereira
authors: Isadora Pozzetti
authors: IP
authors: Siba
authors: Andrea Frozino
authors: AF
authors: Ribeiro
authors: Rosana
authors: R
authors: Camarini
authors: Roseli
authors: R
authors: Boerngen-Lacerda
mesh_terms: D000428:Alcohol Drinking; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D000099052:CRF Receptor, Type 1