title: Binge alcohol drinking by mice requires intact group 1 metabotropic glutamate receptor signaling within the central nucleus of the amygdala.
abstract: Despite the fact that binge alcohol drinking (intake resulting in blood alcohol concentrations (BACs) 80 mg% within a 2-h period) is the most prevalent form of alcohol-use disorders (AUD), a large knowledge gap exists regarding how this form of AUD influences neural circuits mediating alcohol reinforcement. The present study employed integrative approaches to examine the functional relevance of binge drinking-induced changes in glutamate receptors, their associated scaffolding proteins and certain signaling molecules within the central nucleus of the amygdala (CeA). A 30-day history of binge alcohol drinking (for example, 4-5 g kg(-1) per 2 h(-1)) elevated CeA levels of mGluR1, GluN2B, Homer2a/b and phospholipase C (PLC) β3, without significantly altering protein expression within the adjacent basolateral amygdala. An intra-CeA infusion of mGluR1, mGluR5 and PLC inhibitors all dose-dependently reduced binge intake, without influencing sucrose drinking. The effects of co-infusing mGluR1 and PLC inhibitors were additive, whereas those of coinhibiting mGluR5 and PLC were not, indicating that the efficacy of mGluR1 blockade to lower binge intake involves a pathway independent of PLC activation. The efficacy of mGluR1, mGluR5 and PLC inhibitors to reduce binge intake depended upon intact Homer2 expression as revealed through neuropharmacological studies of Homer2 null mutant mice. Collectively, these data indicate binge alcohol-induced increases in Group1 mGluR signaling within the CeA as a neuroadaptation maintaining excessive alcohol intake, which may contribute to the propensity to binge drink.
authors: Department of Behavioral Neuroscience, VA Medical Research, Oregon Health & Science University, Portland, OR, USA.
authors: Debra K
authors: DK
authors: Cozzoli
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Justin
authors: J
authors: Courson
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Melissa G
authors: MG
authors: Wroten
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Daniel I
authors: DI
authors: Greentree
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Emily N
authors: EN
authors: Lum
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Rianne R
authors: RR
authors: Campbell
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Andrew B
authors: AB
authors: Thompson
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Dan
authors: D
authors: Maliniak
authors: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Paul F
authors: PF
authors: Worley
authors: Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors: Georg
authors: G
authors: Jonquieres
authors: Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors: Matthias
authors: M
authors: Klugmann
authors: Department of Behavioral Neuroscience, VA Medical Research, Oregon Health & Science University, Portland, OR, USA.
authors: Deborah A
authors: DA
authors: Finn
authors: Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors: Karen K
authors: KK
authors: Szumlinski
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D063425:Binge Drinking / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D000072233:Homer Scaffolding Proteins; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606625:Homer2 protein, mouse; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
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