title: Repeated cycles of chronic intermittent ethanol exposure in mice increases voluntary ethanol drinking and ethanol concentrations in the nucleus accumbens.
abstract: BACKGROUND
  This study examined the relationship between voluntary ethanol consumption and ethanol concentrations measured in the nucleus accumbens of ethanol dependent and nondependent C57BL/6J mice.
  
  
  METHODS
  Mice were offered ethanol in a two-bottle choice; limited access paradigm and consummatory behavior was monitored with lickometers. After baseline intake stabilized, mice received chronic intermittent ethanol (EtOH group) or air (CTL group) exposure by inhalation (16 h/day for 4 days) and then resumed drinking. Brain ethanol levels during voluntary drinking were measured by microdialysis procedures and compared to brain ethanol concentrations produced during chronic intermittent ethanol vapor exposure.
  
  
  RESULTS
  Voluntary ethanol consumption progressively increased over repeated cycles of chronic intermittent ethanol exposure but remained unchanged in CTL mice. Analysis of lick patterns indicated EtOH mice consumed ethanol at a faster rate compared to CTL mice. The greater and faster rate of ethanol intake in EtOH mice produced higher peak brain ethanol concentrations compared to CTL mice, and these levels were similar to levels produced during chronic intermittent ethanol exposure.
  
  
  CONCLUSIONS
  These results show that in this model of dependence and relapse drinking, dependent mice exhibit enhanced voluntary ethanol consumption relative to nondependent controls, which consequently produces blood and brain ethanol concentrations similar to those experienced during chronic intermittent ethanol exposure.
authors.affiliation: Department of Psychiatry and Behavioral Science, Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Charleston, SC 29425-0742, USA. griffinw@musc.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Griffin
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Lopez
authors.forename: Amy B
authors.initials: AB
authors.lastname: Yanke
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Middaugh
authors.forename: Howard C
authors.initials: HC
authors.lastname: Becker
mesh_terms: D000280:Administration, Inhalation; D000428:Alcohol Drinking; D000818:Animals; D001921:Brain / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012008:Recurrence; D014018:Tissue Distribution
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
references.citation: Alcohol Res Health. 2000;24(2):105-13
references.pmid: 11199277
references.citation: Brain Res. 2007 Mar 23;1138:208-13
references.pmid: 17275791
references.citation: Alcohol Clin Exp Res. 1993 Feb;17(1):94-8
references.pmid: 8452212
references.citation: Alcohol Clin Exp Res. 2007 Jun;31(6):939-49
references.pmid: 17403068
references.citation: Synapse. 2006 Feb;59(2):74-81
references.pmid: 16270301
references.citation: Behav Pharmacol. 1998 Mar;9(2):149-61
references.pmid: 10065934
references.citation: J Neurochem. 1990 Apr;54(4):1449-52
references.pmid: 1690270
references.citation: Psychopharmacology (Berl). 2005 Oct;181(4):688-96
references.pmid: 16001125
references.citation: Nat Neurosci. 2005 Nov;8(11):1442-4
references.pmid: 16251985
references.citation: Alcohol. 1995 May-Jun;12(3):221-6
references.pmid: 7639955
references.citation: J Neurochem. 2000 Oct;75(4):1685-93
references.pmid: 10987851
references.citation: Arch Biochem Biophys. 1989 May 15;271(1):33-9
references.pmid: 2712574
references.citation: Alcohol Clin Exp Res. 2004 Nov;28(11):1676-82
references.pmid: 15547454
references.citation: Alcohol Clin Exp Res. 2004 Dec;28(12):1829-38
references.pmid: 15608599
references.citation: Psychopharmacology (Berl). 2003 Jul;168(3):262-70
references.pmid: 12684735
references.citation: Neuropsychopharmacology. 2000 Jun;22(6):581-94
references.pmid: 10788758
references.citation: Alcohol Clin Exp Res. 1999 Jun;23(6):991-1007
references.pmid: 10397283
references.citation: Alcohol. 2005 Aug;37(1):23-33
references.pmid: 16472716
references.citation: Neuropsychopharmacology. 2001 Feb;24(2):97-129
references.pmid: 11120394
references.citation: Alcohol Clin Exp Res. 2005 Sep;29(9):1630-40
references.pmid: 16205363
references.citation: Mol Cell Biochem. 2006 Jun;286(1-2):171-80
references.pmid: 16652227
references.citation: J Neurosci Methods. 1998 Jan 31;79(1):31-6
references.pmid: 9531457
references.citation: Psychopharmacology (Berl). 1994 Sep;116(1):26-32
references.pmid: 7862927
references.citation: Alcohol Clin Exp Res. 2003 Oct;27(10):1573-82
references.pmid: 14574227
references.citation: Alcohol Clin Exp Res. 2006 Sep;30(9):1500-5
references.pmid: 16930212
references.citation: Alcohol Clin Exp Res. 2003 Feb;27(2):232-43
references.pmid: 12605072