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Early life adversity increases striatal dopamine D1 receptor density and promotes social alcohol drinking in mice, especially males
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  • Published: 15 April 2026

Early life adversity increases striatal dopamine D1 receptor density and promotes social alcohol drinking in mice, especially males

  • Lucy G. Anderson  ORCID: orcid.org/0000-0002-8908-28871,
  • Anna E. Tischer  ORCID: orcid.org/0009-0001-4268-59042,
  • Roland Bock  ORCID: orcid.org/0000-0002-8654-10801,
  • Michael Michaelides  ORCID: orcid.org/0000-0003-0398-49172 &
  • …
  • Veronica A. Alvarez  ORCID: orcid.org/0000-0003-2611-86751 

Translational Psychiatry , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Molecular neuroscience
  • Predictive markers

Abstract

The brain’s reward-processing circuitry remains sensitive to experience throughout early life and into adulthood, allowing individuals to adapt to their unique environments. Adverse experiences early in life can increase vulnerability to substance use disorders, likely through alterations to this circuitry. Yet, the precise neurobiological mechanisms by which early life adversity acts are incompletely characterized. In this study, we used a limited bedding and nesting (LBN) paradigm as a translationally relevant model of early life adversity in isogenic C57BL/6J mice. After LBN-rearing, we assessed the lasting behavioral and neurobiological impacts of this experience in adulthood. In robust sample sizes, our results validated previous findings of increased risk avoidance, enhanced acute locomotor response to alcohol, and greater voluntary alcohol drinking in socially-housed LBN-reared mice, especially males. Further, using autoradiography, we found LBN-reared mice had increased striatal D1-like receptor binding, skewing D1- to D2-like receptor balance relative to cross-fostered controls. However, after voluntary alcohol drinking, we found a strong downregulation in D1-like, and some D2-like, receptor binding, negating pre-existing differences in striatal dopamine receptor binding. We posit that via both transcriptional and post-transcriptional mechanisms, LBN-rearing upregulates striatal D1-receptor density and alters risk avoidance and acute alcohol stimulation to promote alcohol drinking among adversity-exposed mice. Together, these findings reveal specific neurobiological mechanisms that promote alcohol consumption following early life adversity and suggest complex interactions between early life adversity, sex-related factors, and dopamine receptor regulation in contributing to alcohol use disorder (AUD) vulnerability.

Data availability

All data and code are accessible on Mendeley. Reserved: https://doi.org/10.17632/5ygmcc6cm4.2.

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Acknowledgements

We would like to thank the NIMH IRP Rodent Behavioral Core for their help with behavioral testing and Drs. Miriam Bocarsly and Yan Leng for their technical advice. Additionally, we would like to thank Mikal Armstrong, our former HI-STEP 2.0 intern, for her help running IntelliCage experiments. The contributions of the NIH authors were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.

Funding

This work was supported by funding from the NIH Intramural Research Program of the National Institutes of Health to V.A.A. (ZIA AA000421; ZIA MH002987) and to M.M. (ZIA DA000069).

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Authors and Affiliations

  1. Laboratory on Neurobiology of Compulsive Behaviors, National Institute on Mental Health, Intramural Research Program, NIH, Bethesda, MD, 20892, USA

    Lucy G. Anderson, Roland Bock & Veronica A. Alvarez

  2. Biobehavioral Imaging and Molecular Neuropsychopharmacology Section, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA

    Anna E. Tischer & Michael Michaelides

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  1. Lucy G. Anderson
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Contributions

Conceptualized by LGA, VAA, RB, and MM. All experimentation except autoradiography conducted by LGA. Autoradiography conducted by AET. Technical support by RB. Formal analysis by LGA, AET, and RB. Writing and figure design by LGA. Review and editing by all authors. Funding acquisition by VAA and MM.

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Correspondence to Michael Michaelides or Veronica A. Alvarez.

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All experimental procedures were approved by the NIH Institutional Animal Care and Use Committee and complied with Public Health Service policy on the humane care and use of laboratory animals.

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Anderson, L.G., Tischer, A.E., Bock, R. et al. Early life adversity increases striatal dopamine D1 receptor density and promotes social alcohol drinking in mice, especially males. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-04033-2

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  • Received: 18 December 2025

  • Revised: 12 March 2026

  • Accepted: 30 March 2026

  • Published: 15 April 2026

  • DOI: https://doi.org/10.1038/s41398-026-04033-2

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