Evidence map›Paper›PMID 41617925›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026

Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors.

Marsida Kallupi, Giordano de Guglielmo, Lieselot L G Carrette, Sierra Simpson, Jenni Kononoff, Adam Kimbrough, Lauren C Smith, Kokila Shankar, Alicia Avelar, Dana Conlisk and 25 more

Abstract read
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In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Marsida KallupiDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA. mkallupi@health.ucsd.edu.ORCID http://orcid.org/0000-0002-8688-709X
Giordano de GuglielmoDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-4782-7430
Lieselot L G CarretteDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5217-2774
Sierra SimpsonDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Jenni KononoffDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
Adam KimbroughDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9434-4987
Lauren C SmithDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Kokila ShankarDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Alicia AvelarDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Dana ConliskDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-4641-7878
Molly BrennanDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Lani TieuDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Sharona SedighimDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Brent BoomhowerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Lisa MaturinDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
McKenzie J FannonDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Angelica MartinezDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Caitlin CrookDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Selen DirikDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0006-2429-4252
Nathan VelardeDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Paul SchweitzerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Selene Bonnet-ZahediDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0008-8151-4850
Elizabeth SneddonDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4004-9434
Sonja PlasilDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Alex A MorganDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Dyar N OthmanDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Benjamin SichelDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Beverly PengDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Apurva S ChitreDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Oksana PolesskayaDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Justin LauDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Ashley VangDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Leah C Solberg WoodsSection on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Olivier GeorgeDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA. olgeorge@health.ucsd.edu.ORCID http://orcid.org/0000-0002-3700-5003

Funding

Use of Next-Gen Sequencing to Identify Genetic Variants that Influence compulsiveOxycodone Intake in Outbred RatsU01DA044451 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Olivier George, Abraham A Palmer · 2018 to 2026
$7.3M
DP30DA060810 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Abraham A Palmer · 2024 to 2026
$5.6M
Enhancing Addiction Severity Prediction by Modulating GABAergic Activity in the Central Amygdala of RATTACA RatsR21DA062049 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KALLUPI, MARSIDA · 2025 to 2025
$439k
NIDA NIH HHS P30 DA060810NIDA NIH HHS R21 DA062049NIDA NIH HHS U01 DA044451
6 · The paper itself

Abstract

Family and twin studies indicate that 20-60% of the vulnerability to opioid use disorder (OUD) is influenced by genetic factors, but the specific genes driving addiction-like behaviors, including sensitivity to opioid analgesia, tolerance, dependence, and escalation of oxycodone self-administration, remain unidentified, limiting precision medicine approaches. To address this, we phenotyped over 500 heterogeneous stock (HS) rats, an outbred population with high genetic diversity, to characterize traits associated with OUD vulnerability and resilience. Rats self-administered oxycodone (150 µg/kg/infusion) in short-access (2 h/day, 4 days) followed by long-access (12 h/day, 14 days) sessions. We assessed motivation for oxycodone using progressive ratio testing, withdrawal-induced hyperalgesia with von Frey tests, and tolerance to oxycodone's analgesic effects via tail immersion tests. Large cohorts (n = 46-60) and Z-score normalization minimized cohort-specific effects. An Addiction Index, derived from averaging Z-scores of escalation, motivation, tolerance, and hyperalgesia, revealed significant individual variability. Rats with severe addiction-like behaviors displayed higher initial analgesia, greater escalation, and more pronounced tolerance compared to resilient rats. Females showed increased escalation and motivation compared to males, but similar tolerance and hyperalgesia. Principal component analysis confirmed the Addiction Index's validity, accounting for 40% of behavioral variance. This high-throughput phenotyping in HS rats, leveraging their genetic diversity, provides a robust framework for genome-wide association studies to identify gene variants linked to OUD vulnerability, offering translational potential for discovering novel therapeutic targets and advancing pharmacogenetic strategies for OUD treatment.

Indexed as

Analgesics, OpioidBehavior, AddictiveOpioid-Related DisordersOxycodoneAnimalsDrug ToleranceFemaleHyperalgesiaMaleMotivationRatsSelf AdministrationAnalgesics, OpioidOxycodone

Identifiers

PMID41617925
PMCPMC13125645

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.