Lateral habenula-projecting central amygdala circuits expressing GABA and NPY Y1 receptor modulate binge-like ethanol intake in mice.

Autor:	Companion MA; Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Davie Hall, CB#3270, Chapel Hill, NC 27599-3270, United States.; The Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Davie Hall, CB#7178, Chapel Hill, NC 27599-7178, United States., Gonzalez DA; Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Davie Hall, CB#3270, Chapel Hill, NC 27599-3270, United States., Robinson SL; Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Davie Hall, CB#3270, Chapel Hill, NC 27599-3270, United States.; The Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Davie Hall, CB#7178, Chapel Hill, NC 27599-7178, United States., Herman MA; Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Davie Hall, CB#3270, Chapel Hill, NC 27599-3270, United States.; The Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Davie Hall, CB#7178, Chapel Hill, NC 27599-7178, United States.; Department of Pharmacology, University of North Carolina at Chapel Hill, Davie Hall, CB#7365, Chapel Hill, NC 27599-7365, United States., Thiele TE; Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Davie Hall, CB#3270, Chapel Hill, NC 27599-3270, United States.; The Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Davie Hall, CB#7178, Chapel Hill, NC 27599-7178, United States.
Jazyk:	angličtina
Zdroj:	Addiction neuroscience [Addict Neurosci] 2022 Sep; Vol. 3. Date of Electronic Publication: 2022 Apr 30.
DOI:	10.1016/j.addicn.2022.100019
Abstrakt:	The central nucleus of the amygdala (CeA) is a critical brain region in the integration of emotional behaviors and is one of the major output areas of the amygdaloid complex. The CeA is composed of GABAergic interneurons and projection neurons which co-express a range of peptides including neuropeptide Y (NPY). Importantly, GABA and NPY signaling, via the NPY Y1 receptor (Y1R), in the CeA modulate binge-like ethanol intake in rodents and these systems undergo neuroplastic alterations following a history of ethanol consumption. Here we assessed the roles of GABAergic and Y1R+ circuits arising from the CeA and innervating the lateral habenula (LHb), a brain region that modulates the aversive properties of ethanol, in modulating binge-like ethanol intake in mice using "drinking in the dark" (DID) procedures. Using an anterograde cre-inducible reporter virus we established the CeA → LHb circuit in male and female vgat- ires -cre and NPY1r-cre mice. Next, we found that chemogenetic silencing of both the GABAergic or Y1R+ CeA → LHb circuit significantly blunted binge-like intake of a 20% ethanol solution but this same procedure failed to alter the consumption of a 3% sucrose solution. Finally, one, 4-day cycle of DID failed to alter basal or effects of ethanol or NPY on inhibitory transmission in Y1R+ CeA → LHb neurons. The present results suggest that blunting GABAergic tone in LHb-projecting CeA neurons may represent a new approach to preventing the development of AUDs. Drugs that target NPY Y1Rs are potential attractive targets. Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests. Dr. Thiele owns shares of Glauser Life Sciences, a copy the aims to develop therapeutics for mental health disorders. The work that is presented in this paper is not directly related to the scientific aims of Glauser Life Sciences.
Databáze:	MEDLINE
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