Evidence map›Paper›PMID 36456196›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2023

Delta Opioid Receptor-Mediated Antidepressant-Like Effects of Diprenorphine in Mice.

Keith M Olson, Todd M Hillhouse, Gwendolyn E Burgess, Joshua L West, James E Hallahan, Isaac J Dripps, Allison G Ladetto, Kenner C Rice, Emily M Jutkiewicz, John R Traynor

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

Article in The Journal of pharmacology and experimental therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  5. Review
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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 1 institution in 1 country.

Keith M OlsonDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
Todd M HillhouseDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
Gwendolyn E BurgessDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
Joshua L WestDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
James E HallahanDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
Isaac J DrippsDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
Allison G LadettoDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
Kenner C RiceDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).ORCID 0000-0002-1147-9147
Emily M JutkiewiczDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.).
John R TraynorDepartment of Pharmacology and Edward F Domino Research Center (K.M.O., T.M.H., G.E.B., J.L.W., J.E.H., I.J.D., A.G.L., E.M.J., J.R.T.) and Department of Medicinal Chemistry (J.R.T.), University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin (T.M.H.); and Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.) jtraynor@umich.edu.ORCID 0000-0002-1849-8316
University of Wisconsin–Green Bay · 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
POSTDOCTORAL TRAINING IN THE BIOLOGY OF DRUG ABUSET32DA007268 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TRAYNOR, JOHN R. · 1991 to 2021
$6.7M
Allosteric Modulation of the Mu-Opioid ReceptorR37DA039997 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TRAYNOR, JOHN R. · 2015 to 2024
$6.4M
NIDA Training Program in Neuroscience-Administrative SupplementT32DA007281 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Shelly Beth Flagel · 1995 to 2026
$5.7M
Abuse potential of a novel bifunctional opioid ligandR21DA041565 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JUTKIEWICZ, EMILY M · 2017 to 2018
$427k
NIDA NIH HHS R21 DA041565NIDA NIH HHS R37 DA039997NIDA NIH HHS T32 DA007268NIDA NIH HHS T32 DA007281
6 · The paper itself

Abstract

Major depressive disorder is a highly common disorder, with a lifetime prevalence in the United States of approximately 21%. Traditional antidepressant treatments are limited by a delayed onset of action and minimal efficacy in some patients. Ketamine is effective and fast-acting, but there are concerns over its abuse liability. Thus, there is a need for safe, fast-acting antidepressant drugs. The opioid buprenorphine shows promise but also has abuse liability due to its mu-agonist component. Preclinical evidence indicates that the delta-opioid system contributes to mood disorders, and delta-opioid agonists are effective in preclinical models of depression- and anxiety-like states. In this study, we test the hypothesis that the mu-opioid antagonist diprenorphine by virtue of its partial delta opioid agonist activity may offer a beneficial profile for an antidepressant medication without abuse liability. Diprenorphine was confirmed to bind with high affinity to all three opioid receptors, and functional experiments for G protein activation verified diprenorphine to be a partial agonist at delta- and kappa-opioid receptors and a mu-antagonist. Studies in C57BL/6 mice demonstrated that an acute dose of diprenorphine produced antidepressant-like effects in the tail suspension test and the novelty-induced hypophagia test that were inhibited in the presence of the delta-selective antagonist, naltrindole. Diprenorphine did not produce convulsions, a side effect of many delta agonists but rather inhibited convulsions caused by the full delta agonist SNC80; however, diprenorphine did potentiate pentylenetetrazole-induced convulsions. Diprenorphine, and compounds with a similar pharmacological profile, may provide efficient and safe rapidly acting antidepressants. SIGNIFICANCE STATEMENT: The management of major depressive disorder, particularly treatment-resistant depression, is a significant unmet medical need. Here we show that the opioid diprenorphine, a compound with mu-opioid receptor antagonist activity and delta- and kappa-opioid receptor partial agonist activities, has rapid onset antidepressant-like activity in animal models. Diprenorphine and compounds with a similar pharmacological profile to diprenorphine should be explored as novel antidepressant drugs.

Indexed as

Analgesics, OpioidDiprenorphineMajor Depressive DisorderAnimalsAntidepressive AgentsMiceMice, Inbred C57BLReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, muSeizuresAnalgesics, OpioidAntidepressive AgentsDiprenorphineReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, mu

Identifiers

PMID36456196
PMCPMC9976798
OpenAlexW4310592547

What OpenQuestion holds

Textmetadata
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.