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On the early life origins of vulnerability to opioid addiction

Molecular Psychiatry volume 26, pages 4409–4416 (2021)Cite this article

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Abstract

The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA interacts with factors such as increased access to opioids to directly influence brain development and function, and cause opioid addiction vulnerability, is unknown. We simulated ELA in female rats and this led to a striking opioid addiction-like phenotype. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of a less salient natural reward was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction.

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Fig. 1: Early life adversity potentiates heroin-seeking behaviors.
Fig. 2: Early life adversity increases demand for opioids and highly palatable food.

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Data availability

The data forming the basis of these studies do not include genomic or imaging data sets storable in public repositories. Data will be readily made available when requested from the authors.

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Acknowledgements

We thank the National Institute on Drug Abuse (NIDA) Drug Supply Program (Research Triangle Park, NC, USA), for providing heroin and remifentanil.

Funding

The research was supported in part by NIH grants MH096889; NS28912; DA035251; DA044118; GM008620; MH119049 and the Hewitt Foundation for Biomedical Research

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Authors and Affiliations

  1. Department of Neurobiology & Behavior, University of California—Irvine, Irvine, CA, USA

    Sophia C. Levis, Christina R. Perrone & Stephen V. Mahler

  2. Department of Anatomy & Neurobiology, University of California—Irvine, Irvine, CA, USA

    Sophia C. Levis, Jenny Molet, Jessica L. Bolton & Tallie Z. Baram

  3. Department of Psychiatry, Stanford University, Stanford, CA, USA

    Brandon S. Bentzley

  4. Department of Pediatrics, University of California—Irvine, Irvine, CA, USA

    Tallie Z. Baram

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  1. Sophia C. Levis
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Correspondence to Tallie Z. Baram or Stephen V. Mahler.

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Levis, S.C., Bentzley, B.S., Molet, J. et al. On the early life origins of vulnerability to opioid addiction. Mol Psychiatry 26, 4409–4416 (2021). https://doi.org/10.1038/s41380-019-0628-5

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