Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice
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.
Authors
- Ashna Singh
- Colleen K. Hadley (ORCID: https://orcid.org/0000-0002-9402-4462)
- Jacqueline Welday (ORCID: https://orcid.org/0000-0003-0151-7418)
- Peter Bellotti (ORCID: https://orcid.org/0000-0001-9367-5100)
- Dezhi Liu (ORCID: https://orcid.org/0000-0002-9636-9966)
- Peter U. Hámor (ORCID: https://orcid.org/0000-0002-7728-8933)
- Irena Pigulevskiy (ORCID: https://orcid.org/0000-0002-1166-0464)
- Jean K. Rivera-Irizarry (ORCID: https://orcid.org/0000-0002-5703-8531)
- Joseph Asfouri (ORCID: https://orcid.org/0000-0002-2683-2564)
- Mary Jane Skelly
- David W. Erikson (ORCID: https://orcid.org/0000-0002-3383-9297)
- Olivia B. Levine (ORCID: https://orcid.org/0000-0003-1315-8360)
- Kristen E. Pleil (ORCID: https://orcid.org/0000-0001-6300-9414)
- Lia J. Zallar (ORCID: https://orcid.org/0000-0003-0749-5205)
- John D. Miller (ORCID: https://orcid.org/0000-0002-7206-9846)
- Jacob B. Geri (ORCID: https://orcid.org/0000-0002-9215-5610)
- Kristopher M. Fecteau (ORCID: https://orcid.org/0000-0001-5747-2912)
- Pasha Ghazal (ORCID: https://orcid.org/0000-0002-1934-4482)
- Lauren V. Hollmer
- Ana-Sofia Rico Rozo
- Scottie Nelson
- Rebecca Bender
- Hajar Mehanna
Institutions
- Oregon National Primate Research Center (US)
- COMSATS University Islamabad (PK)
- Iona College (US)
- Cornell University (US)
- Tri-Institutional PhD Program in Chemical Biology (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-54737-6
- Citations
- 13
- Primary Topic
- Estrogen and related hormone effects
- Type
- article
- Field-Weighted Citation Impact
- 7.15
Funders
- National Alliance for Research on Schizophrenia and Depression
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Weill Cornell Medical College
- National Institute of General Medical Sciences