Evidence map›Paper›PMID 35915264›Full record

ArticlePsychopharmacology2022

A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice.

Mackenzie C Gamble, Byron Chuan, Teresa Gallego-Martin, Micah A Shelton, Stephanie Puig, Christopher P O'Donnell, Ryan W Logan

Open access · greenAbstract read
In one paragraph

Article in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Mackenzie C GambleDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, 02118, USA.
Byron ChuanDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Teresa Gallego-MartinDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Micah A SheltonDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Stephanie PuigDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, 02118, USA.
Christopher P O'DonnellDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Ryan W LoganDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, 02118, USA. rwlogan@bu.edu.
University of Pittsburgh · USBoston University · US

Funding

Cell-type specific role of circadian-dependent transcription in fentanyl-induced synaptic and behavioral plasticity - SupplementR01HL150432 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LOGAN, RYAN W · 2019 to 2020
$2.0M
Molecular rhythm alterations in human post-mortem brain associated with opioid use disorderR01DA051390 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOGAN, RYAN W, SENEY, MARIANNE L · 2020 to 2023
$1.9M
Generating novel mouse tools to investigate brain region and cell-type specific circadian molecular mechanisms of reward and motivationR33DA041872 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOGAN, RYAN W, MCCLUNG, COLLEEN A · 2018 to 2020
$1.1M
The role of the circadian transcription factor NPAS2 in the nucleus accumbens to regulate cocaine rewardK01DA038654 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOGAN, RYAN W · 2015 to 2018
$626k
Generating novel mouse tools to investigate brain region and cell-type specific circadian molecular mechanisms of reward and motivationR21DA041872 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOGAN, RYAN W, MCCLUNG, COLLEEN A · 2016 to 2017
$379k
NHLBI NIH HHS R01 HL150432NIDA NIH HHS K01 DA038654NIDA NIH HHS R01 DA051390NIDA NIH HHS R21 DA041872NIDA NIH HHS R33 DA041872
6 · The paper itself

Abstract

rationaleSynthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations.

objectivesTo determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.

methodsElectroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.

resultsAcute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.

conclusionsChronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.

Indexed as

FentanylTranscription FactorsAnalgesics, OpioidAnimalsArousalBasic Helix-Loop-Helix ProteinsCircadian RhythmElectroencephalographyEye MovementsMaleMiceNerve Tissue ProteinsSleepWakefulnessAnalgesics, OpioidBasic Helix-Loop-Helix ProteinsFentanylNerve Tissue ProteinsNpas2 protein, mouseTranscription FactorsCircadian genesCircadian rhythmsFentanylNon-rapid eye movement sleepNPAS2OpioidsSleepWithdrawal

Identifiers

PMID35915264
PMCPMC10925970
OpenAlexW4289277824

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.