Binge alcohol drinking by mice requires intact group1 metabotropic glutamate receptor signaling within the Central nucleus of the Amygdale

Debra K. Cozzoli, Justin Courson, Melissa G. Wroten, Daniel I. Greentree, Emily N. Lum, Rianne R. Campbell, Andrew B. Thompson, Dan Maliniak, Paul F. Worley, Georg Jonquieres, Matthias Klugmann, Deborah A. Finn, Karen K. Szumlinski

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)435-444
Number of pages10
JournalNeuropsychopharmacology
Volume39
Issue number2
DOIs
StatePublished - Jan 2014

Keywords

  • Homer
  • binge drinking
  • central nucleus of the amygdala
  • glutamate
  • metabotropic glutamate receptor
  • phospholipaseC

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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