Evidence map›Paper›PMID 40884023›Full record

ArticleAlcohol, clinical & experimental research2025

Neuropeptide Y1 receptor expressing circuit from the central amygdala to lateral hypothalamus modulates binge-like ethanol consumption in a sex-dependent manner.

Sophie C Bendrath, Ashlyn Stone, Anne M Dankert, Todd E Thiele

Abstract read
In one paragraph

Article in Alcohol, clinical & experimental research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Sophie C BendrathDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Ashlyn StoneDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Anne M DankertDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-3046-504X
Todd E ThieleDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0001-8908-9256

Funding

Training on Research in Drug AbuseT32DA007244 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Regina M Carelli · 1990 to 2026
$7.6M
Neuropeptide Y: Role in Ethanol Intake and SensitivityR01AA013573 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI THIELE, TODD ERIC · 2001 to 2018
$3.8M
The role of corticotropin releasing factor in binge-like ethanol drinkingR01AA022048 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash, TODD Eric THIELE · 2013 to 2026
$3.2M
The role of brainstem norepinephrine in binge alcohol drinking and taste aversionR01AA025809 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TODD Eric THIELE, Montserrat Navarro Thiele · 2018 to 2026
$3.1M
Neuropeptide Y: Role in Ethanol Intake and SensitivityR37AA013573 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TODD Eric THIELE · 2019 to 2026
$3.0M
NIAAA NIH HHS AA013573NIAAA NIH HHS AA022048NIAAA NIH HHS AA025809NIAAA NIH HHS R01 AA013573NIAAA NIH HHS R01 AA022048NIAAA NIH HHS R01 AA025809NIAAA NIH HHS R37 AA013573NIDA NIH HHS DA007244NIDA NIH HHS T32 DA007244
6 · The paper itself

Abstract

backgroundAlcohol use disorder is characterized by maladaptive patterns of alcohol consumption, with emerging evidence suggesting that neuropeptide Y (NPY) signaling through Y1 and Y2 receptors (Y1R and Y2R) within the central amygdala (CeA) plays a critical role in modulating ethanol intake. The current experiments investigate the neural mechanisms underlying binge-like ethanol drinking, focusing on the involvement of Y1R+ CeA-to-lateral hypothalamus (LH) projections, dynamic interactions between Y1R and Y2R within the CeA, and the impact of chronic ethanol exposure on Y1R protein expression.

methodsNPY1R-ires-cre mice received LH cannulation, were infused with cre-dependent inhibitory (Gi) Designer Receptor Exclusively Activated by Designer Drug (DREADD) or control virus into the CeA, and went through drinking in the dark (DID). Other animals were treated intra-CeA with an NPY overexpression vector (FIB-NPY) or control, and went through DID, intermittent access to ethanol (IAE), and open-field testing. Viral placements and receptor targets were assessed via qPCR. Finally, mice went through six cycles of DID, and Y1R immunohistochemical (IHC) labeling on neurons was assessed for animals sacrificed after the final DID session or after a 24-h period of abstinence.

resultsChemogenetic inhibition of Y1R+ CeA-LH projections selectively reduced binge-like ethanol drinking in male mice without affecting female mice. Viral NPY overexpression revealed behavioral effects and predictive relationships between receptor mRNA expression and intake patterns. Although no significant differences were found in Y1R/NeuN colocalization across sex and treatment groups, correlational analyses revealed that Y1R expression varied with individual ethanol consumption.

conclusionsCollectively, these results support a model wherein Y1R signaling within the CeA regulates ethanol consumption through circuit-specific mechanisms and broader neuroadaptive changes influenced by sex and individual drinking patterns. This research advances our understanding of the neurobiological mechanisms underlying binge-like ethanol intake and highlights the complex, sex-dependent roles of NPY-Y1R and Y2R signaling in the CeA.

Indexed as

Alcohol DrinkingBinge DrinkingCentral Amygdaloid NucleusHypothalamic Area, LateralReceptors, Neuropeptide YSex CharacteristicsAnimalsEthanolFemaleMaleMiceMice, Inbred C57BLMice, TransgenicNeuropeptide YSex FactorsEthanolNeuropeptide Yneuropeptide Y-Y1 receptorNpy1r protein, mouseReceptors, Neuropeptide YDREADDsdrinking in the darkneuropeptide YNPY overexpressionsex differences

Identifiers

PMID40884023
PMCPMC12519052

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.