Opioid drug seeking after early-life adversity: a role for delta opioid receptors

Sophia C. Levis; Matthew T. Birnie; Yiyan Xie; Noriko Kamei; Puja V. Kulkarni; Johanna S. Montesinos; Christina R. Perrone; Catherine M. Cahill; Tallie Z. Baram; Stephen V. Mahler

Addiction Neuroscience (Dec 2024)

Opioid drug seeking after early-life adversity: a role for delta opioid receptors

Sophia C. Levis,
Matthew T. Birnie,
Yiyan Xie,
Noriko Kamei,
Puja V. Kulkarni,
Johanna S. Montesinos,
Christina R. Perrone,
Catherine M. Cahill,
Tallie Z. Baram,
Stephen V. Mahler

Affiliations

Sophia C. Levis: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA; Department of Neurobiology & Behavior, University of California Irvine, Irvine, CA, USA; Department of Psychiatry and Human Behavior, University of California Irvine School of Medicine, Orange, CA, USA; Corresponding author at: University of California Irvine, 1132 McGaugh Hall, Irvine, CA 92697, USA.
Matthew T. Birnie: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA; Department of Pediatrics, University of California Irvine, Irvine, CA, USA
Yiyan Xie: Department of Pediatrics, University of California Irvine, Irvine, CA, USA
Noriko Kamei: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA
Puja V. Kulkarni: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA
Johanna S. Montesinos: Department of Neurobiology & Behavior, University of California Irvine, Irvine, CA, USA
Christina R. Perrone: Department of Neurobiology & Behavior, University of California Irvine, Irvine, CA, USA
Catherine M. Cahill: Department of Psychiatry and Biobehavioral Sciences, Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Tallie Z. Baram: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA; Department of Pediatrics, University of California Irvine, Irvine, CA, USA
Stephen V. Mahler: Department of Neurobiology & Behavior, University of California Irvine, Irvine, CA, USA

Journal volume & issue: Vol. 13
p. 100175

Abstract

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Opioid use disorder (OUD) is associated with a history of early-life adversity (ELA), an association that is particularly strong in women. In a rodent model, we previously found that ELA enhances risk for opioid addiction selectively in females, but the mechanisms for this effect are unclear. Here, we show that ELA robustly alters cFos responses to opioid drugs in females’ nucleus accumbens (NAc) and basolateral amygdala (BLA), but not elsewhere. We further identify delta opioid receptors (DOR), which mature in the first week of life and thus later than kappa or mu opioid receptors, as a potential mediator of ELA's impacts on reward circuit functions. Accordingly, DOR mRNA in NAc was persistently reduced in adult females with ELA history. Moreover, pharmacological stimulation of NAc DORs increased opioid demand in control females (recapitulating the ELA phenotype), while blocking DORs in ELA females conversely reduced high-effort drug consumption, simulating the control rearing phenotype. These findings support a role for NAc DORs in mediating ELA-induced opioid vulnerability. In contrast, BLA neurons expressing DOR protein do not overlap heroin- responsive cells in ELA rats, arguing against a direct relationship of BLA DORs to heroin's addiction-relevant actions in the brain. Together, these results suggest a novel and selective role for NAc DORs in contributing to enduring, ELA-provoked vulnerability to OUD.

Published in Addiction Neuroscience

ISSN: 2772-3925 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/addiction-neuroscience

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