Evidence map›Paper›PMID 32006048›Full record

ArticlePsychopharmacology2020

Kappa opioid agonists reduce oxycodone self-administration in male rhesus monkeys.

C Austin Zamarripa, Jennifer E Naylor, Sally L Huskinson, E Andrew Townsend, Thomas E Prisinzano, Kevin B Freeman

Open access · greenAbstract read
In one paragraph

Article in Psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 6% of its field
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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. A review of the kappa opioid receptor system in opioid use.Neuroscience and biobehavioral reviews · 2024
    Pooled it
  3. Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. 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

6 authors at 4 institutions in 1 country.

C Austin ZamarripaDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, The University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Jennifer E NaylorBoozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
Sally L HuskinsonDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, The University of Mississippi Medical Center, Jackson, MS, 39216, USA.
E Andrew TownsendDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Thomas E PrisinzanoDepartment of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536, USA.
Kevin B FreemanDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, The University of Mississippi Medical Center, Jackson, MS, 39216, USA. kfreeman@umc.edu.ORCID http://orcid.org/0000-0003-3389-6555
University of Mississippi Medical Center · USUniversity of Arkansas for Medical Sciences · USUniversity of Kentucky · USVirginia Commonwealth University · US

Funding

Investigation of Neoclerodanes as Novel Opioid LigandsR01DA018151 · NIDA · UNIVERSITY OF KENTUCKY · PI PRISINZANO, THOMAS EDWARD · 2005 to 2020
$5.7M
Deterrents for prescription opioid abuseR01DA039167 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI FREEMAN, KEVIN B. · 2015 to 2025
$4.9M
Unpredictable availability as a determinant of drug-related outcomesR01DA045011 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI HUSKINSON, SALLY · 2018 to 2022
$1.8M
Therapeutic selectivity of biased mu-opioid agonists.F31DA048586 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI ZAMARRIPA, CARLOS AUSTIN · 2019 to 2021
$82k
NIDA NIH HHS DA018151NIDA NIH HHS DA045011NIDA NIH HHS F31 DA048586NIDA NIH HHS F31DA048586NIDA NIH HHS R01 DA018151NIDA NIH HHS R01 DA039167NIDA NIH HHS R01DA039167NIDA NIH HHS R01 DA045011
6 · The paper itself

Abstract

rationaleCombinations of mu and kappa opioid receptor (KOR) agonists have been proposed as potential analgesic formulations with reduced abuse liability. The current studies extend previous work by investigating the typical KOR agonist, salvinorin A, and the atypical KOR agonist, nalfurafine, as deterrents of oxycodone self-administration using a progressive ratio (PR) schedule of reinforcement.

methodsIn separate experiments, adult male rhesus monkeys (N = 4/experiment) were trained under a PR schedule of reinforcement to self-administer cocaine (0.1 mg/kg/injection) and saline on alternating days. Oxycodone (0.01-0.1 mg/kg/injection) alone and combined with salvinorin A (experiment 1; 0.006, 0.012 mg/kg/injection) or nalfurafine (experiment 2; 0.0001-0.00032 mg/kg/injection) were tested within the alternating cocaine and saline baseline. The mechanism of nalfurafine's effects on oxycodone self-administration was investigated via pretreatment with the KOR antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg; i.m.).

resultsAll subjects self-administered oxycodone alone above saline levels at sufficiently large doses, and combining salvinorin A or nalfurafine with oxycodone reduced the mean number of injections per session to saline levels (experiment 1) or to levels that were significantly lower than oxycodone alone (experiment 2). The ability of nalfurafine to reduce oxycodone self-administration was reversed by pretreatment with nor-BNI.

conclusionsThese results demonstrate that KOR agonists, including the clinically used KOR agonist, nalfurafine, can punish self-administration of a prescription opioid analgesic, oxycodone, in rhesus monkeys and that nalfurafine's punishing effect is KOR-dependent. Combinations of KOR agonists with prescription opioids may have reduced abuse liability.

Indexed as

Analgesics, OpioidAnimalsBehavior, AddictiveCocaineDiterpenes, ClerodaneDose-Response Relationship, DrugMacaca mulattaMaleMorphinansNaltrexoneNarcotic AntagonistsOxycodoneReceptors, Opioid, kappaReinforcement, PsychologySelf AdministrationSpiro CompoundsAnalgesics, OpioidCocaineDiterpenes, ClerodaneMorphinansNaltrexoneNarcotic AntagonistsnorbinaltorphimineOxycodoneReceptors, Opioid, kappasalvinorin ASpiro CompoundsTRK 820Kappa opioid agonistOxycodonePunishmentRhesus monkeySelf-administration

Identifiers

PMID32006048
PMCPMC7196516
OpenAlexW3003349663

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.