Nucleus Accumbens Shell Orexin-1 Receptors Are Critical Mediators of Binge Intake in Excessive-Drinking Individuals

Frontiers in Neuroscience
Kelly LeiFrederic Woodward Hopf

Abstract

Excessive, binge alcohol drinking is a potent and pernicious obstacle to treating alcohol use disorder (AUD), and heavy-drinking humans are responsible for much of the substantial costs and harms of AUD. Thus, identifying key mechanisms that drive intake in higher-drinking individuals may provide important, translationally useful therapeutic interventions. Orexin-1-receptors (Ox1Rs) promote states of high motivation, and studies with systemic Ox1R inhibition suggest a particular role in individuals with higher intake levels. However, little has been known about circuits where Ox1Rs promote pathological intake, especially excessive alcohol consumption. We previously discovered that binge alcohol drinking requires Ox1Rs in medial nucleus accumbens shell (Shell), using two-bottle-choice Drinking-in-the-Dark (2bc-DID) in adult, male C57BL/6 mice. Here, we show that Shell Ox1Rs promoted intake during intermittent-access alcohol drinking as well as 2bc-DID, and that Shell inhibition with muscimol/baclofen also suppressed 2bc-DID intake. Importantly, with this large data set, we were able to demonstrate that Shell Ox1Rs and overall activity were particularly important for driving alcohol consumption in higher-drinking individuals, wit...Continue Reading

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Citations

Jan 4, 2020·Neurochemical Research·Santosh Kumar PrajapatiAlakh N Sahu
Feb 20, 2021·Alcoholism, Clinical and Experimental Research·Rishi SharmaMahesh Thakkar
May 1, 2021·International Journal of Molecular Sciences·Anna K RadkeFrederic W Hopf
Jun 3, 2021·International Journal of Molecular Sciences·Jeffrey L BarrEugen Brailoiu
Jun 26, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Thatiane De Oliveira SergioFrederic W Hopf

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Methods Mentioned

BETA
pharmacotherapies

Software Mentioned

Prism ( GraphPad )
SPSS
R
R Foundation for Statistical Computing

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