title: Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of the Amygdala Mediates Binge Alcohol Consumption.
abstract: BACKGROUND
  Protein kinase C epsilon (PKCε) is emerging as a potential target for the development of pharmacotherapies to treat alcohol use disorders, yet little is known regarding how a history of a highly prevalent form of drinking, binge alcohol intake, influences enzyme priming or the functional relevance of kinase activity for excessive alcohol intake.
  
  
  METHODS
  Immunoblotting was employed on tissue from subregions of the nucleus accumbens (NAc) and the amygdala to examine both idiopathic and binge drinking-induced changes in constitutive PKCε priming. The functional relevance of PKCε translocation for binge drinking and determination of potential upstream signaling pathways involved were investigated using neuropharmacologic approaches within the context of two distinct binge drinking procedures, drinking in the dark and scheduled high alcohol consumption.
  
  
  RESULTS
  Binge alcohol drinking elevated p(Ser729)-PKCε levels in both the NAc and the central nucleus of the amygdala (CeA). Moreover, immunoblotting studies of selectively bred and transgenic mouse lines revealed a positive correlation between the propensity to binge drink alcohol and constitutive p(Ser729)-PKCε levels in the NAc and CeA. Finally, neuropharmacologic inhibition of PKCε translocation within both regions reduced binge alcohol consumption in a manner requiring intact group 1 metabotropic glutamate receptors, Homer2, phospholipase C, and/or phosphotidylinositide-3 kinase function.
  
  
  CONCLUSIONS
  Taken together, these data indicate that PKCε signaling in both the NAc and CeA is a major contributor to binge alcohol drinking and to the genetic propensity to consume excessive amounts of alcohol.
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California; Department of Behavioral Neuroscience, Oregon Health & Science University and Portland Alcohol Research Center, Veterans Affairs Portland Healthcare System, Portland, Oregon.
authors: Debra K
authors: DK
authors: Cozzoli
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Justin
authors: J
authors: Courson
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Charlotte
authors: C
authors: Rostock
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Rianne R
authors: RR
authors: Campbell
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Melissa G
authors: MG
authors: Wroten
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Hadley
authors: H
authors: McGregor
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Amanda L
authors: AL
authors: Caruana
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
authors: Bailey W
authors: BW
authors: Miller
authors: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Jia-Hua
authors: JH
authors: Hu
authors: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Ping
authors: P
authors: Wu Zhang
authors: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Bo
authors: B
authors: Xiao
authors: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Paul F
authors: PF
authors: Worley
authors: Department of Behavioral Neuroscience, Oregon Health & Science University and Portland Alcohol Research Center, Veterans Affairs Portland Healthcare System, Portland, Oregon.
authors: John C
authors: JC
authors: Crabbe
authors: Department of Behavioral Neuroscience, Oregon Health & Science University and Portland Alcohol Research Center, Veterans Affairs Portland Healthcare System, Portland, Oregon.
authors: Deborah A
authors: DA
authors: Finn
authors: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California. Electronic address: szumlinski@psych.ucsb.edu.
authors: Karen K
authors: KK
authors: Szumlinski
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000378:metabolism*; D066274:Central Amygdaloid Nucleus / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009714:Nucleus Accumbens / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D000431:Ethanol; C497256:Prkce protein, mouse; D051744:Protein Kinase C-epsilon
keywords: Alcohol use disorders; Drinking in the dark; Glutamate; HDID-1 mice; Homer; Scheduled high alcohol consumption