Evidence map›Paper›PMID 40494620›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2025

Phospho-CREB Regulation on NMDA Glutamate Receptor 2B and Mitochondrial Calcium Uniporter in the Ventrolateral Periaqueductal Gray Controls Chronic Morphine Withdrawal in Male Rats.

Hyun Yi, Jun Gu, Peter J Hamilton, Shue Liu, Shoumin Zhu, Daigo Ikegami, Kentaro Hayashi, Yuta Kashiwagi, Takafumi Iida, Qiaofeng Liu and 9 more

Abstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 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

19 authors.

Hyun YiDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Jun GuDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Peter J HamiltonNash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.ORCID 0000-0002-6819-8346
Shue LiuDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Shoumin ZhuDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.
Daigo IkegamiDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Kentaro HayashiDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Yuta KashiwagiDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Takafumi IidaDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Qiaofeng LiuDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Xun ZhuDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Xiaoying TongDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Dunfa PengDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.
Gerald Z ZhuangDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Marta PardoDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Wael El-RifaiDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.
Roy C LevittDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Eric J NestlerNash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.ORCID 0000-0002-7905-2000
Shuanglin HaoDepartment of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136 shao@med.miami.edu.ORCID 0000-0003-2435-1473

Funding

Transcription Factors in Stimulant and Opioid ActionP01DA047233 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI YASMIN L. HURD · 2019 to 2026
$16.5M
MOLECULAR STUDIES OF COCAINE ACTION IN BRAINR37DA007359 · NIDA · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1996 to 2020
$6.9M
Molecular Studies of Cocaine Action in BrainR01DA007359 · NIDA · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1991 to 2025
$5.6M
Role of Gut Microbiome in HIV/Opioid Induced Peripheral NeuropathyR01DA047089 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HAO, SHUANGLIN, RAMAKRISHNAN, SUNDARAM · 2018 to 2022
$2.3M
A new pathway of spinal neurons in neuropathic pain induced by HIV with opioidR01DA047157 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HAO, SHUANGLIN · 2018 to 2022
$2.1M
The role of NRF2 in reflux-induced esophageal adenocarcinomasR01CA224366 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI EL-RIFAI, WAEL · 2018 to 2022
$1.7M
Neuropathic mechanisms and gene therapy on opioid dependenceR01DA034749 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HAO, SHUANGLIN · 2014 to 2018
$1.7M
Using CRISPR tools to uncover the role of CREB-gene regulation in drug abuseR00DA045795 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAMILTON, PETER JAMES · 2020 to 2022
$739k
Engineering CRISPR constructs to elucidate the causal contribution of cell-type specific, gene-targeted CREB binding to the pathogenesis of drug abuseK99DA045795 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAMILTON, PETER JAMES · 2018 to 2019
$354k
Gene therapy of HIV-neuropathic pain with morphine toleranceR03DA026734 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HAO, SHUANGLIN · 2009 to 2010
$309k
Transgene for morphine tolerance and withdrawalR03DA020078 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HAO, SHUANGLIN · 2005 to 2005
$77k
BLRD VA I01 BX005114NCI NIH HHS R01 CA224366NIDA NIH HHS K99 DA045795NIDA NIH HHS P01 DA047233NIDA NIH HHS R00 DA045795NIDA NIH HHS R01 DA007359NIDA NIH HHS R01 DA034749NIDA NIH HHS R01 DA047089NIDA NIH HHS R01 DA047157NIDA NIH HHS R03 DA020078NIDA NIH HHS R03 DA026734NIDA NIH HHS R37 DA007359
6 · The paper itself

Abstract

Opioid use disorder (OUD) is a chronic disease of the brain, and it currently continues at crisis proportions in the United States. Opioid physical withdrawal is a major driver of compulsive drug-taking behavior, triggering short-term relapse of opioid addiction. Early pharmacological evidence shows that midbrain periaqueductal gray (PAG) plays an important role in morphine withdrawal (MW). However, we still know few details about the underlying molecular mechanisms. Improving our understanding of such mechanisms will enable increasingly safe and effective treatments for patients with OUD. Here, MW was induced by the naloxone precipitation after chronic intraperitoneal administration of morphine for a period of 5 d in Sprague Dawley male rats. MW increased phosphorylation of cAMP response element binding protein (pCREB, a primary marker of CREB functional activation), NMDA glutamate receptor 2B subunit (NR2B), and mitochondrial calcium uniporter (MCU) within the ventrolateral PAG (vlPAG). Inhibition of pCREB, NR2B, or MCU within this brain region reduced the severity of MW. Chromatin immunoprecipitation (ChIP) assay and luciferase report assay demonstrated that pCREB mediated the transcription of the

Indexed as

Calcium ChannelsCyclic AMP Response Element-Binding ProteinMorphinePeriaqueductal GrayReceptors, N-Methyl-D-AspartateSubstance Withdrawal SyndromeAnimalsMalePhosphorylationRatsRats, Sprague-DawleyCalcium ChannelsCyclic AMP Response Element-Binding Proteinmitochondrial calcium uniporterMorphineNR2B NMDA receptorReceptors, N-Methyl-D-AspartateMCUmorphine withdrawalNR2BpCREBvlPAG

Identifiers

PMID40494620
PMCPMC12268980

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.