title: The circadian Per1 and Per2 genes influence alcohol intake, reinforcement, and blood alcohol levels.
abstract: BACKGROUND
  Perturbations in the function of core circadian clock components such as the Period (Per) family of genes are associated with alcohol use disorder, and disruptions in circadian cycles may contribute to alcohol abuse and relapse. This study tested ethanol consumption, reinforcement, and metabolism in mice containing functional mutations in Per1 and/or Per2 genes on an ethanol-preferring background, C57BL/6J mice.
  
  
  METHODS
  Mice were tested in: (A) free-access intake with ascending concentrations of ethanol (2-16%, v/v), (B) conditioned place preference using ethanol (2g/kg for males; 2.5g/kg for females) vs. saline injections, (C) recovery of the righting reflex following a 4g/kg bolus of ethanol, and (D) blood ethanol levels 1h after a 2g/kg bolus of ethanol.
  
  
  RESULTS
  All Per mutant (mPer) mice showed increased ethanol intake and condition place preference compared to controls. There were also genotypic differences in blood ethanol concentration: in males, only mPer1 mice showed a significantly higher blood ethanol concentration than WT mice, but in females, all mPer mice showed higher blood ethanol levels than WT mice.
  
  
  CONCLUSIONS
  Mutation of either Per1 or Per2, as well as mutations of both genes, increases ethanol intake and reinforcement in an ethanol-preferring mouse model. In addition, this increase in ethanol seeking behavior seems to result both from a change in ethanol metabolism and a change in reward responding to ethanol, but not from any change in sensitivity to ethanol's sedating effects.
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth, United States.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gamsby
authors.forename: E L
authors.initials: EL
authors.lastname: Templeton
authors.forename: L A
authors.initials: LA
authors.lastname: Bonvini
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: Loros
authors.forename: J C
authors.initials: JC
authors.lastname: Dunlap
authors.forename: A I
authors.initials: AI
authors.lastname: Green
authors.forename: D
authors.initials: D
authors.lastname: Gulick
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D057897:Reflex, Righting / Q000187:drug effects / Q000502:physiology; D012054:Reinforcement, Psychology
chemical_list: C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D000431:Ethanol