title: Alcohol in excess: CRF₁ receptors in the rat and mouse VTA and DRN.
abstract: BACKGROUND
  Manipulation of the stress neuropeptide corticotropin-releasing factor (CRF), specifically central antagonism of the type 1 receptors (CRF-R1), effectively reduces alcoholic-like ethanol drinking in rodents. Escalated consumption is largely controlled by neurocircuitry that is important for reward and affect, such as the ventral tegmental area (VTA) and the dorsal raphé nucleus (DRN).
  
  
  OBJECTIVE
  The current studies investigated the role of CRF-R1 within the VTA and DRN and their relation to escalated ethanol drinking in two species. An additional goal was to explore whether high alcohol-drinking individuals would be more affected by CRF-R1 antagonism than low alcohol-drinking individuals.
  
  
  METHODS
  With a two-bottle choice drinking procedure, adult male C57BL/6J mice and Long-Evans rats were given 24-h access to 20 % ethanol and water on an intermittent schedule. Rats and mice were implanted with cannulae targeting the VTA or DRN. Doses of the CRF-R1 antagonist CP-154,526 (butyl-[2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine)) were microinfused to modulate drinking of ethanol and water over the course of 24 h.
  
  
  RESULTS
  In both mice and rats, intra-VTA CP-154,526 selectively decreased ethanol intake, while identical doses (0.3 and 0.6 μg) infused intra-DRN reduced both ethanol and water drinking. Long-Evans rats displayed a range of individual differences for ethanol preference, and CP-154,526 suppressed ethanol drinking in the high-preferring animals regardless of brain site manipulation.
  
  
  CONCLUSIONS
  The current findings confirm previous studies that blockade of CRF-R1 efficaciously reduces escalated drinking while also suggesting that the effects of intermittent access on alcohol consumption may require CRF interaction with dopamine in the VTA.
authors.affiliation: Department of Psychology, Tufts University, 530 Boston Avenue, Medford, MA 02155, USA. lara.hwa@tufts.edu
authors.forename: Lara S
authors.initials: LS
authors.lastname: Hwa
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Debold
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology / Q000517:prevention & control*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013045:Species Specificity; D017557:Ventral Tegmental Area / 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