title: Nucleus accumbens mGluR5-associated signaling regulates binge alcohol drinking under drinking-in-the-dark procedures.
abstract: BACKGROUND
  Alcohol increases the expression of Group 1 metabotropic glutamate receptors (mGluRs) and their associated scaffolding protein Homer2 and stimulates phosphatidylinositol 3-kinase (PI3K) within the nucleus accumbens (NAC). Moreover, functional studies suggest that NAC Group 1 mGluR/Homer2/PI3K signaling may be a potential target for pharmacotherapeutic intervention in alcoholism.
  
  
  METHODS
  Immunoblotting was conducted to examine the effects of alcohol consumption under drinking-in-the-dark (DID) procedures on Group 1 mGluR-associated proteins in C57BL/6J (B6) mice. Follow-up behavioral studies examined the importance of Group 1 mGluR/Homer2/PI3K signaling within the NAC shell for limited-access alcohol drinking. Finally, immunoblotting examined whether the NAC expression of Group 1 mGluR-associated proteins is a genetic correlate of high alcohol drinking using a selectively bred high DID (HDID-1) mouse line.
  
  
  RESULTS
  Limited-access alcohol drinking under DID procedures up-regulated NAC shell Homer2 levels, concomitant with increases in mGluR5 and NR2B. Intra-NAC shell blockade of mGluR5, Homer2, or PI3K signaling, as well as transgenic disruption of the Homer binding site on mGluR5, decreased alcohol consumption in B6 mice. Moreover, transgenic disruption of the Homer binding site on mGluR5 and Homer2 deletion both prevented the attenuating effect of mGluR5 and PI3K blockade upon intake. Finally, the basal NAC shell protein expression of mGluR1 and Homer2 was increased in offspring of HDID-1 animals.
  
  
  CONCLUSIONS
  Taken together, these data further implicate Group 1 mGluR signaling through Homer2 within the NAC in excessive alcohol consumption.
authors.affiliation: Department of Psychological and Brain Sciences, The Neuroscience Research Institute, University of California, Santa Barbara, USA.
authors.forename: Debra K
authors.initials: DK
authors.lastname: Cozzoli
authors.forename: Justin
authors.initials: J
authors.lastname: Courson
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Caruana
authors.forename: Bailey W
authors.initials: BW
authors.lastname: Miller
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Greentree
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Thompson
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Wroten
authors.forename: Ping-Wu
authors.initials: PW
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Hu
authors.forename: Matthias
authors.initials: M
authors.lastname: Klugmann
authors.forename: Pamela
authors.initials: P
authors.lastname: Metten
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.forename: John C
authors.initials: JC
authors.lastname: Crabbe
authors.forename: Karen K
authors.initials: KK
authors.lastname: Szumlinski
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics; D002492:Central Nervous System Depressants / Q000097:blood; D000431:Ethanol / Q000097:blood; D000072233:Homer Scaffolding Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D018092:Kainic Acid Receptors / Q000235:genetics* / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D000431:Ethanol; D000072233:Homer Scaffolding Proteins; D019869:Phosphatidylinositol 3-Kinases; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C000606625:Homer2 protein, mouse; C121001:NR2B NMDA receptor