Evidence map›Paper›PMID 29572653›Full record

ArticlePsychopharmacology2018

Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.

Katherine Cone, Janell Lanpher, Abigail Kinens, Philomena Richard, Sarah Couture, Rebecca Brackin, Emily Payne, Kylee Harrington, Kenner C Rice, Glenn W Stevenson

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Fentanyl Research: Key to Fighting the Opioid Crisis.Journal of clinical medicine · 2025
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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

10 authors at 2 institutions in 1 country.

Katherine ConeDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Janell LanpherDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Abigail KinensDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Philomena RichardDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Sarah CoutureDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Rebecca BrackinDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Emily PayneDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Kylee HarringtonDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA.
Kenner C RiceDrug Design and Synthesis Section, Molecular Targets and Medications Branch, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, 20850, USA.
Glenn W StevensonDepartment of Psychology, University of New England, Biddeford, ME, 04005, USA. gstevenson@une.edu.
University of New England · USNational Institute on Alcohol Abuse and Alcoholism · US

Funding

Medicinal Chemistry of Drugs Acting on Central and Peripheral Opioid ReceptorsZIADA000527 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI RICE, KENNER · 2009 to 2025
$23.2M
Tissue resident macrophages in sensory ganglia: function and impact on nociceptionP20GM103643 · NIGMS · UNIVERSITY OF NEW ENGLAND · PI MENG, IAN D · 2012 to 2021
$20.9M
Measurement of pain-suppressed behaviors in rodent models of chronic painR15AR054975 · NIAMS · UNIVERSITY OF NEW ENGLAND · PI STEVENSON, GLENN W. · 2007 to 2014
$579k
NIAMS NIH HHS R15 AR054975NIGMS NIH HHS P20 GM103643
6 · The paper itself

Abstract

RATIONALE AND

objectivesAlthough delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior.

methodsA mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced a dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects.

conclusionsThe therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.

Indexed as

Therapeutic IndexAnalgesics, OpioidAnimalsBenzamidesConditioning, OperantDose-Response Relationship, DrugMaleMethadonePainPiperazinesRatsRats, Sprague-DawleyReceptors, Opioid, deltaReceptors, Opioid, mu4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamideAnalgesics, OpioidBenzamidesMethadonePiperazinesReceptors, Opioid, deltaReceptors, Opioid, muOperant conditioningOpioid receptor interactionsPain-depressed behaviorsRatsSNC80

Identifiers

PMID29572653
PMCPMC5924452
OpenAlexW2792276963

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.