title: Blockade of the corticotropin releasing factor type 1 receptor attenuates elevated ethanol drinking associated with drinking in the dark procedures.
abstract: BACKGROUND
  Drinking in the dark (DID) procedures have recently been developed to induce high levels of ethanol drinking in C57BL/6J mice, which result in blood ethanol concentrations (BECs) reaching levels that have measurable affects on physiology and/or behavior. The present experiments determined whether the increased ethanol drinking caused by DID procedures can be attenuated by pretreatment with CP-154,526; a corticotropin releasing factor type-1 (CRF1) receptor antagonist.
  
  
  METHODS
  In Experiment 1, male C57BL/6J mice received ethanol (20% v/v) in place of water for 4 hours, beginning with 3 hours into the dark cycle. On the fourth day, mice were given an intraperitoneal injection of one of the 4 doses of CP-154,526 (0, 1, 3, 10 mg/kg) 30 minutes before receiving their ethanol bottle. In Experiment 2, C57BL/6J mice had 2 hours of access to the 20% ethanol solution, beginning with 3 hours into the dark cycle on days 1 to 3, and 4 hours of access to the ethanol bottle on day 4 of DID procedures. Mice were given an intraperitoneal injection of one of the 4 doses of CP-154,526 (0, 1, 3, 10 mg/kg) 30 minutes before receiving their ethanol bottle on day 4. Tail blood samples were collected immediately after the 4-hour ethanol access period on the fourth day of each experiment. Additional control experiments assessed the effects of CP-154,526 on 4-hour consumption of a 10% (w/v) sucrose solution and open-field locomotor activity.
  
  
  RESULTS
  In Experiment 1, the vehicle-treated group consumed approximately 4.0 g/kg/4 h of ethanol and achieved BECs of approximately 30 mg%. Furthermore, pretreatment with the CRF1 receptor antagonist did not alter ethanol consumption. On the other hand, procedures used in Experiment 2 resulted in vehicle-treated mice consuming approximately 6.0 g/kg/4 h of ethanol with BECs of about 80 mg%. Additionally, the 10 mg/kg dose of CP-154,526 significantly reduced ethanol consumption and BECs to approximately 3.0 g/kg/4 h and 27 mg%, respectively, relative to vehicle-treated mice. Importantly, the 10 mg/kg dose of the CRF1R antagonist did not significantly alter 4-hour sucrose consumption or locomotor activity.
  
  
  CONCLUSIONS
  These data indicate that CRF1R signaling modulates high, but not moderate, levels of ethanol drinking associated with DID procedures.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599-3270, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Sparta
authors.forename: Angela M
authors.initials: AM
authors.lastname: Sparrow
authors.forename: Emily G
authors.initials: EG
authors.lastname: Lowery
authors.forename: Jon R
authors.initials: JR
authors.lastname: Fee
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Knapp
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology*; 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