IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57880-w.html
   My bibliography  Save this article

Midbrain ghrelin receptor signalling regulates binge drinking in a sex specific manner

Author

Listed:
  • Amy J. Pearl

    (Florey Institute of Neuroscience and Mental Health)

  • Xavier J. Maddern

    (Florey Institute of Neuroscience and Mental Health
    University of Melbourne)

  • Paulo Pinares-Garcia

    (Florey Institute of Neuroscience and Mental Health)

  • Lauren T. Ursich

    (Florey Institute of Neuroscience and Mental Health
    University of Melbourne)

  • Roberta G. Anversa

    (Florey Institute of Neuroscience and Mental Health
    University of Melbourne)

  • Arnav Shesham

    (Florey Institute of Neuroscience and Mental Health
    Monash University)

  • Robyn M. Brown

    (Florey Institute of Neuroscience and Mental Health
    University of Melbourne)

  • Felicia M. Reed

    (Monash University)

  • William J. Giardino

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Andrew J. Lawrence

    (Florey Institute of Neuroscience and Mental Health
    University of Melbourne)

  • Leigh C. Walker

    (Florey Institute of Neuroscience and Mental Health
    University of Melbourne)

Abstract

Risky drinking rates are rising, particularly in women, yet sex as a biological variable has only recently gained traction. The centrally projecting Edinger-Westphal (EWcp) nucleus has emerged as a key regulator of alcohol consumption. Here we found that EWcppeptidergic cells reduce binge drinking specifically in female mice. We show this effect is mediated by the ghrelin receptor (GHSR), with EWcppeptidergic inhibition blocking ghrelin-induced drinking and Ghsr knockdown in EWcppeptidergic, but not EWcpglutamatergic or ventral tegmental area cells, reducing binge drinking in females, independent of circulating sex hormones. Female mice showed higher EWcp Ghsr expression, and EWcppeptidergic neurons were more sensitive to ghrelin. Moreover, intra-EWcp delivery of GHSR inverse agonist and antagonist reduced binge drinking, suggesting direct actions of ghrelin. These findings highlight the EWcp as a critical mediator of excessive alcohol consumption via GHSR in female mice, offering insights into the ghrelin system’s role in alcohol consumption.

Suggested Citation

  • Amy J. Pearl & Xavier J. Maddern & Paulo Pinares-Garcia & Lauren T. Ursich & Roberta G. Anversa & Arnav Shesham & Robyn M. Brown & Felicia M. Reed & William J. Giardino & Andrew J. Lawrence & Leigh C., 2025. "Midbrain ghrelin receptor signalling regulates binge drinking in a sex specific manner," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57880-w
    DOI: 10.1038/s41467-025-57880-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57880-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57880-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. M. E. Flanigan & O. J. Hon & S. D’Ambrosio & K. M. Boyt & L. Hassanein & M. Castle & H. L. Haun & M. M. Pina & T. L. Kash, 2023. "Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Masayasu Kojima & Hiroshi Hosoda & Yukari Date & Masamitsu Nakazato & Hisayuki Matsuo & Kenji Kangawa, 1999. "Ghrelin is a growth-hormone-releasing acylated peptide from stomach," Nature, Nature, vol. 402(6762), pages 656-660, December.
    3. Matthias Tschöp & David L. Smiley & Mark L. Heiman, 2000. "Ghrelin induces adiposity in rodents," Nature, Nature, vol. 407(6806), pages 908-913, October.
    4. Michelle L Johnson & M Jill Saffrey & Victoria J Taylor, 2016. "Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-12, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. repec:plo:pone00:0035708 is not listed on IDEAS
    2. Michelle L Johnson & M Jill Saffrey & Victoria J Taylor, 2016. "Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-12, November.
    3. repec:plo:pone00:0065422 is not listed on IDEAS
    4. Amany M Basuny & Moustafa A AboelAnin & Eman A Hamed, 2020. "Structure and Physiological Functions of Ghrelin," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 31(2), pages 24085-24092, October.
    5. K. Tanaka & T. Takizawa & O. Oki & K. Fukawa & T. Ito & M. Miyabe & H. Mannen & Y. Kurosawa & K. Hirose, 2015. "Allele frequency for c.335 A>C polymorphisms in porcine ghrelin/obestatin prepropeptide gene and association analysis with performance traits in various pig breeds," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 60(9), pages 411-416.
    6. Qian Wang, 2017. "The Ghrelin/GHS-R1a Pathway is Involved in the Mechanism of the CTA-regulated Neuronal Loop," International Journal of Sciences, Office ijSciences, vol. 6(01), pages 64-72, January.
    7. A. Lotfi & H. Aghdam-Shahryar & J. Ghiasi-Ghalehkandi & H. Kaiya & N. Maheri-Sis, 2011. "Effect of in ovo ghrelin administration on subsequent serum insulin and glucose levels in newly-hatched chicks," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 56(8), pages 377-380.
    8. Sarah M. Mohr & Rafael Dai Pra & Maryann P. Platt & Viktor V. Feketa & Marya Shanabrough & Luis Varela & Ashley Kristant & Haoran Cao & Dana K. Merriman & Tamas L. Horvath & Sviatoslav N. Bagriantsev , 2024. "Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Meng Zhang & Liu Yang & Xue Mi & Gonghui Hu & Yingchang Lu & Chen Wang & Jie Yang & Xiaomin Sun & Minglu Niu & Xianchao Li & Sihan Wang & Jingsai Zhang & Hanbing Yu & Yuyang Wang & Ming Yu & Nan Li & , 2025. "GHS-R1a signaling drives anxiety-related behavior by shaping excitability of ventromedial hypothalamic neurons," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    10. Nan Li, 2016. "Ghrelin/GHS-R1a Signaling Modulates Emotional Learning and Memory," International Journal of Sciences, Office ijSciences, vol. 5(03), pages 160-163, March.
    11. Mohammed Saeed Al-Ayed & Khaled Sadeq Al-Shaibari & Dhafer Alshehri & Mohammed Jamaan Alzahrani & Iman Nasser & Hamdan Saad Alaamri & Wed Ahmad Alaseeri & Ahmed A. Mahfouz & Saeed Ali Alsareii & Ahmed, 2020. "Serum Ghrelin Levels in Saudi Obese Asthmatic School-Children—Correlation with Interleukin-4, Interleukin-5, and Interleukin-21," IJERPH, MDPI, vol. 17(5), pages 1-11, March.
    12. Gerrit Vortmeier & Stephanie H DeLuca & Sylvia Els-Heindl & Constance Chollet & Holger A Scheidt & Annette G Beck-Sickinger & Jens Meiler & Daniel Huster, 2015. "Integrating Solid-State NMR and Computational Modeling to Investigate the Structure and Dynamics of Membrane-Associated Ghrelin," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-28, March.
    13. Andrea Palermo & Dario Tuccinardi & Giuseppe Defeudis & Mikiko Watanabe & Luca D’Onofrio & Angelo Lauria Pantano & Nicola Napoli & Paolo Pozzilli & Silvia Manfrini, 2016. "BMI and BMD: The Potential Interplay between Obesity and Bone Fragility," IJERPH, MDPI, vol. 13(6), pages 1-30, May.
    14. Nazan Yurtcu & Canan Soyer Caliskan & Huri Guvey & Samettin Celik & Safak Hatirnaz & Andrea Tinelli, 2022. "Predictive and Diagnostic Value of Serum Adipokines in Pregnant Women with Intrahepatic Cholestasis," IJERPH, MDPI, vol. 19(4), pages 1-13, February.
    15. Mahalaqua Nazli Khatib & Anuraj Shankar & Richard Kirubakaran & Kingsley Agho & Padam Simkhada & Shilpa Gaidhane & Deepak Saxena & Unnikrishnan B & Dilip Gode & Abhay Gaidhane & Syed Quazi Zahiruddin, 2015. "Effect of Ghrelin on Mortality and Cardiovascular Outcomes in Experimental Rat and Mice Models of Heart Failure: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-21, May.
    16. Enrica Bianchi & Kim Boekelheide & Mark Sigman & Susan J Hall & Kathleen Hwang, 2017. "Ghrelin modulates testicular damage in a cryptorchid mouse model," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-17, May.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57880-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.