Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice

Kush Purohit, Puja K. Parekh, Joseph Kern, Ryan W. Logan, Zheng Liu, Yanhua Huang, Colleen A. McClung, John Jr Crabbe, Angela Ozburn

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Chronic alcohol intake leads to long-lasting changes in reward- and stress-related neuronal circuitry. The nucleus accumbens (NAc) is an integral component of this circuitry. Here, we investigate the effects of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) on neuronal activity in the NAc and binge-like drinking. Methods: C57BL/6J mice were stereotaxically injected with AAV2 hSyn-HA hM3Dq, -hM4Di, or -eGFP bilaterally into NAc [core + shell, core or shell]. We measured clozapine-n-oxide (CNO)-induced changes in NAc activity and assessed binge-like ethanol (EtOH) or tastant/fluid intake in a limited access Drinking in the Dark (DID) schedule. Results: We found that CNO increased NAc firing in hM3Dq positive cells and decreased firing in hM4Di cells, confirming the efficacy of these channels to alter neuronal activity both spatially and temporally. Increasing NAc core + shell activity decreased binge-like drinking without altering intake of other tastants. Increasing activity specifically in the NAc core reduced binge-like drinking, and decreasing activity in the NAc core increased drinking. Manipulation of NAc shell activity did not alter DID. Thus, we find that increasing activity in the entire NAc, or just the NAc core is sufficient to decrease binge drinking. Conclusions: We conclude that the reduction in EtOH drinking is not due to general malaise, altered perception of taste, or reduced calorie-seeking. Furthermore, we provide the first evidence for bidirectional control of NAc core and binge-like drinking. These findings could have promising implications for treatment.

Original languageEnglish (US)
Pages (from-to)879-888
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume42
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • Alcohol
  • Binge Drinking
  • DREADDs
  • Nucleus Accumbens Shell or Core

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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