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Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice

Author

Listed:
  • Lia J. Zallar

    (Cornell University)

  • Jean K. Rivera-Irizarry

    (Cornell University)

  • Peter U. Hamor

    (Cornell University)

  • Irena Pigulevskiy

    (Cornell University)

  • Ana-Sofia Rico Rozo

    (Cornell University)

  • Hajar Mehanna

    (Cornell University)

  • Dezhi Liu

    (Cornell University)

  • Jacqueline P. Welday

    (Cornell University)

  • Rebecca Bender

    (Cornell University)

  • Joseph J. Asfouri

    (Cornell University)

  • Olivia B. Levine

    (Cornell University)

  • Mary Jane Skelly

    (Cornell University
    Iona University)

  • Colleen K. Hadley

    (Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program)

  • Kristopher M. Fecteau

    (Oregon National Primate Research Center)

  • Scottie Nelson

    (Cornell University)

  • John Miller

    (Cornell University)

  • Pasha Ghazal

    (Cornell University
    COMSATS University Islamabad (CUI))

  • Peter Bellotti

    (Cornell University)

  • Ashna Singh

    (Cornell University)

  • Lauren V. Hollmer

    (Cornell University)

  • David W. Erikson

    (Oregon National Primate Research Center)

  • Jacob Geri

    (Cornell University)

  • Kristen E. Pleil

    (Cornell University
    Cornell University
    Cornell University)

Abstract

Ovarian-derived estrogen can signal non-canonically at membrane-associated receptors in the brain to rapidly regulate neuronal function. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high estrogen levels, but a causal role for estrogen in driving alcohol drinking has not been established. We found that female mice displayed greater binge alcohol drinking and reduced avoidance when estrogen was high during the estrous cycle than when it was low. The pro-drinking, but not anxiolytic, effect of high endogenous estrogen occurred via rapid signaling at membrane-associated estrogen receptor alpha in the bed nucleus of the stria terminalis, which promoted synaptic excitation of corticotropin-releasing factor neurons and facilitated their activity during alcohol drinking. Thus, this study demonstrates a rapid, nongenomic signaling mechanism for ovarian-derived estrogen in the brain controlling behavior in gonadally intact females.

Suggested Citation

  • Lia J. Zallar & Jean K. Rivera-Irizarry & Peter U. Hamor & Irena Pigulevskiy & Ana-Sofia Rico Rozo & Hajar Mehanna & Dezhi Liu & Jacqueline P. Welday & Rebecca Bender & Joseph J. Asfouri & Olivia B. L, 2024. "Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54737-6
    DOI: 10.1038/s41467-024-54737-6
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