Evidence map›Paper›PMID 39019389›Full record

ArticleBiological psychiatry2025

A Novel Role for the Histone Demethylase JMJD3 in Mediating Heroin-Induced Relapse-Like Behaviors.

Swarup Mitra, Craig T Werner, Treefa Shwani, Ana Garcia Lopez, Dale Federico, Kate Higdon, Xiaofang Li, Pedro H Gobira, Shruthi A Thomas, Jennifer A Martin and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

17 authors.

Swarup MitraDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Craig T WernerDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Treefa ShwaniDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Ana Garcia LopezDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Dale FedericoDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Kate HigdonDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Xiaofang LiDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Pedro H GobiraDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Shruthi A ThomasDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Jennifer A MartinDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Chunna AnDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York.
Ramesh ChandraDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland.
Ian MazeNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Rachel NeveGene Technology Core, Massachusetts General Hospital, Cambridge, Massachusetts.
Mary Kay LoboDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland.
Amy M GancarzDepartment of Psychology, California State University, Bakersfield, Bakersfield, California.
David M DietzDepartment of Pharmacology and Toxicology, Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York. Electronic address: ddietz@buffalo.edu.

Funding

Contributions of aberrant synaptic protein monoaminylation to opiate use disorderR01DA056595 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DAVID M DIETZ, Ian S. Maze · 2022 to 2026
$3.5M
Heroin-Induced genomic regulation of Ventral Pallidum neuron subtypesU01DA051947 · NIDA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI AMENT, SETH ABRAMS, DIETZ, DAVID M · 2020 to 2024
$3.1M
Heroin-induced plasticity: the role of actin dynamicsR01DA046818 · NIDA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI DIETZ, DAVID M · 2019 to 2024
$1.8M
Neuron Subtype Translatomics in Opiate AbuseR21DA048554 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI DIETZ, DAVID M, LOBO, MARY KAY · 2019 to 2020
$445k
A novel role for Oligodendrocyte Progenitor Cells (OPC) in opiate addictionF99NS108543 · NINDS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MARTIN, JENNIFER · 2018 to 2018
$30k
NIDA NIH HHS R01 DA046818NIDA NIH HHS R01 DA056595NIDA NIH HHS R21 DA048554NIDA NIH HHS U01 DA051947NINDS NIH HHS F99 NS108543
6 · The paper itself

Abstract

backgroundEpigenetic changes that lead to long-term neuroadaptations following opioid exposure are not well understood. We examined how histone demethylase JMJD3 in the nucleus accumbens (NAc) influences heroin seeking after abstinence from self-administration.

methodsMale Sprague Dawley rats were trained to self-administer heroin. Western blotting and quantitative polymerase chain reaction were performed to quantify JMJD3 and bone morphogenetic protein (BMP) pathway expression in the NAc (n = 7-11/group). Pharmacological inhibitors or viral expression vectors were microinfused into the NAc to manipulate JMJD3 or the BMP pathway member SMAD1 (n = 9-11/group). The RiboTag capture method (n = 3-5/group) and viral vectors (n = 7-8/group) were used in male transgenic rats to identify the contributions of D1- and D2-expressing medium spiny neurons in the NAc. Drug seeking was tested by cue-induced response previously paired with drug infusion.

resultsLevels of JMJD3 and phosphorylated SMAD1/5 in the NAc were increased after 14 days of abstinence from heroin self-administration. Pharmacological and virus-mediated inhibition of JMJD3 or the BMP pathway attenuated cue-induced seeking. Pharmacological inhibition of BMP signaling reduced JMJD3 expression and H3K27me3 levels. JMJD3 bidirectionally affected seeking: expression of the wild-type increased cue-induced seeking whereas expression of a catalytic dead mutant decreased it. JMJD3 expression was increased in D2

conclusionsJMJD3 mediates persistent cellular and behavioral adaptations that underlie heroin relapse, and this activity is regulated by the BMP pathway.

Indexed as

Drug-Seeking BehaviorHeroinHeroin DependenceJumonji Domain-Containing Histone DemethylasesNucleus AccumbensAnimalsBone Morphogenetic ProteinsMaleRatsRats, Sprague-DawleyRats, TransgenicReceptors, Dopamine D1Receptors, Dopamine D2RecurrenceSelf AdministrationSignal TransductionBone Morphogenetic ProteinsHeroinJumonji Domain-Containing Histone DemethylasesKdm6b protein, ratReceptors, Dopamine D1Receptors, Dopamine D2Cell-type specificityCue-induced heroin seekingHeroinHistone demethylaseNucleus accumbens

Identifiers

PMID39019389
PMCPMC12185243

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.