title: Deletion of Prkcz increases intermittent ethanol consumption in mice.
abstract: BACKGROUND
  Prkcz has been identified as a gene whose expression is positively correlated with ethanol (EtOH) consumption in mice and is also induced by EtOH. Two proteins are produced from Prkcz: protein kinase M zeta (PKMζ), which is expressed in the nervous system and protein kinase C zeta (PKCζ), which is expressed in other tissues. We examined Prkcz(-/-) mice that lack PKCζ and PKMζ to investigate the role of this gene in behavioral responses to EtOH.
  
  
  METHODS
  Male Prkcz(-/-) and wild-type littermates were tested for EtOH consumption using 4 procedures: 24-hour intermittent access, 4-hour limited intermittent access, 4-day drinking-in-the-dark, and 24-hour continuous access. We also assessed the acute hypnotic effect of EtOH, EtOH reward, and taste preference for sweet-, bitter-, salty-, and umami-flavored solutions. Finally, we determined whether EtOH could increase PKMζ and PKCζ transcripts and protein expression in wild-type mice using quantitative PCR and Western blot analysis.
  
  
  RESULTS
  Prkcz(-/-) mice consumed more EtOH than their wild-type littermates in both intermittent access procedures, but not in the drinking-in-the-dark or 24-hour continuous access procedures. EtOH exposure increased Prkcz transcripts in cultured PC12 cells, and intermittent EtOH consumption increased PKMζ protein in the ventral striatum of wild-type mice.
  
  
  CONCLUSIONS
  Absence of PKMζ in the brain is associated with increased EtOH intake during procedures that incorporate intermittent consumption sessions every other day. Our data suggest that EtOH induces PKMζ, which acts in a negative feedback loop to limit binge-like EtOH consumption.
authors.affiliation: Department of Neurology, Ernest Gallo Clinic & Research Center, University of California at San Francisco, Emeryville, California.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lee
authors.forename: Mimi E
authors.initials: ME
authors.lastname: Zou
authors.forename: Jana P
authors.initials: JP
authors.lastname: Lim
authors.forename: Jackie
authors.initials: J
authors.lastname: Stecher
authors.forename: Thomas
authors.initials: T
authors.lastname: McMahon
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016716:PC12 Cells; D011493:Protein Kinase C / Q000172:deficiency* / Q000235:genetics; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D000099221:Protein Kinase C zeta
chemical_list: D000431:Ethanol; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta
keywords: Alcohol Consumption; Knockout Mice; Protein Kinase C Zeta; Protein Kinase M Zeta; Reward; Ventral Striatum
references.citation: Neuropsychopharmacology. 2006 Feb;31(2):396-405
references.pmid: 16034441
references.citation: Nat Rev Neurosci. 2009 Dec;10(12):850-60
references.pmid: 19927149
references.citation: J Neurosci. 2002 Oct 1;22(19):8676-83
references.pmid: 12351742
references.citation: J Neurosci. 2000 May 15;20(10):RC75
references.pmid: 10783399
references.citation: Physiol Behav. 2005 Jan 31;84(1):53-63
references.pmid: 15642607
references.citation: J Neurosci. 2011 Apr 6;31(14):5436-46
references.pmid: 21471379
references.citation: J Neurosci Res. 2001 Jan 15;63(2):200-8
references.pmid: 11169630
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6368-73
references.pmid: 16618939
references.citation: Physiol Genomics. 2010 May;41(3):232-43
references.pmid: 20145204
references.citation: Physiol Rev. 2009 Apr;89(2):649-705
references.pmid: 19342616
references.citation: J Biol Chem. 2003 Oct 10;278(41):40305-16
references.pmid: 12857744
references.citation: Nat Neurosci. 1999 Nov;2(11):997-1002
references.pmid: 10526339
references.citation: Nat Genet. 1998 Feb;18(2):136-41
references.pmid: 9462741
references.citation: Nat Rev Neurosci. 2011 Jan;12(1):9-15
references.pmid: 21119699
references.citation: Nature. 2013 Jan 17;493(7432):420-3
references.pmid: 23283174
references.citation: J Biol Chem. 2012 Apr 13;287(16):12879-85
references.pmid: 22378786
references.citation: Alcohol Clin Exp Res. 2011 Nov;35(11):1938-47
references.pmid: 21631540
references.citation: Nature. 2013 Jan 17;493(7432):416-9
references.pmid: 23283171
references.citation: J Mol Neurosci. 2012 Jul;47(3):546-53
references.pmid: 22127928
references.citation: Brain Behav. 2012 Jan;2(1):22-31
references.pmid: 22574271
references.citation: Science. 2006 Aug 25;313(5790):1141-4
references.pmid: 16931766
references.citation: Hippocampus. 2010 Jun;20(6):691-5
references.pmid: 19806657
references.citation: J Neurosci. 2009 Oct 28;29(43):13494-502
references.pmid: 19864562
references.citation: Alcohol Clin Exp Res. 2011 Apr;35(4):659-70
references.pmid: 21223303
references.citation: Nature. 1998 Nov 26;396(6709):366-9
references.pmid: 9845072
references.citation: J Neurosci. 2004 Nov 17;24(46):10542-52
references.pmid: 15548669
references.citation: Hippocampus. 2012 Mar;22(3):648-9
references.pmid: 21956821
references.citation: Science. 2007 Aug 17;317(5840):951-3
references.pmid: 17702943
references.citation: Alcohol. 1992 Mar-Apr;9(2):155-60
references.pmid: 1599627
references.citation: PLoS One. 2011;6(6):e21568
references.pmid: 21747912
references.citation: Neuropharmacology. 2012 Jun;62(8):2480-8
references.pmid: 22616110
references.citation: J Neurosci. 2008 Jul 30;28(31):7820-7
references.pmid: 18667614
references.citation: J Biochem. 2003 Jan;133(1):1-7
references.pmid: 12761192
references.citation: J Neurosci. 2000 May 1;20(9):3157-64
references.pmid: 10777779
references.citation: Alcohol Alcohol. 2012 Sep-Oct;47(5):509-17
references.pmid: 22717273
references.citation: PLoS Biol. 2008 Dec 23;6(12):2698-706
references.pmid: 19108606