Evidence map›Paper›PMID 41634169›Full record

ArticlePsychopharmacology2026

Repeated fentanyl abstinence intensifies opioid withdrawal and induces a proinflammatory state in striatal microglia.

David J Bergkamp, Kevin R Coffey, Aliyah J Dawkins, Madelyn T Rice, Ari M Peden-Asarch, John F Neumaier

Abstract read
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In one paragraph

Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

David J BergkampDepartment of Pharmacology, University of Washington School of Medicine, Box 357280, Seattle, WA, 98215-7280, USA.
Kevin R CoffeyDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Box 356560, Seattle, WA, 98195-6560, USA.
Aliyah J DawkinsVA Puget Sound Health Care System, VISN 20 Mental Illness Research, Education and Clinical Center, 1660 S Columbia Way, Seattle, WA, 98108, USA.
Madelyn T RiceDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Box 356560, Seattle, WA, 98195-6560, USA.
Ari M Peden-AsarchDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Box 356560, Seattle, WA, 98195-6560, USA.
John F NeumaierDepartment of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Box 356560, Seattle, WA, 98195-6560, USA. neumaier@uw.edu.

Funding

TRAINING IN THE MOLECULAR PHARMACOLOGY OF ABUSED DRUGST32DA007278 · NIDA · UNIVERSITY OF WASHINGTON · PI Susan Marie Ferguson, Paul E. M. Phillips · 1993 to 2026
$9.8M
Microglia and Opioid Withdrawal: Mechanisms of Negative ReinforcementR01DA052618 · NIDA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI NEUMAIER, JOHN F · 2021 to 2025
$1.9M
Reimbursement request for attending the Meeting of the Jointly Sponsored Institutional Predoctoral Training in the Neurosciences T32 Program Directors in Baltimore, MD on 2/19/19T32NS099578 · NINDS · UNIVERSITY OF WASHINGTON · PI SULLIVAN, JANE M, WONG, RACHEL O · 2016 to 2020
$1.4M
University of Washington Significant Opportunities in Addiction Research (UW-SOAR) Neuroscience Doctoral Readiness ProgramR25DA057786 · NIDA · UNIVERSITY OF WASHINGTON · PI FERGUSON, SUSAN MARIE, PHILLIPS, PAUL E. M. · 2022 to 2025
$1.4M
Determining if Activity in Specific Lateral Habenula Output Pathways Motivates Avoidance of Synthetic Opioid Withdrawal or Cue Induced ReinstatementR00DA052571 · NIDA · UNIVERSITY OF WASHINGTON · PI Kevin R. Coffey · 2024 to 2026
$746k
Microglia and Opioid WithdrawalR21DA044757 · NIDA · UNIVERSITY OF WASHINGTON · PI NEUMAIER, JOHN F · 2017 to 2018
$388k
NIDA NIH HHS R00 DA052571NIDA NIH HHS R00DA052571NIDA NIH HHS R01 DA052618NIDA NIH HHS R01DA052618NIDA NIH HHS R21 DA044757NIDA NIH HHS R25 DA057786NIDA NIH HHS R25DA057786NIDA NIH HHS T32 DA007278NIDA NIH HHS T32DA007278NINDS NIH HHS T32 NS099578
6 · The paper itself

Abstract

rationaleOpioid withdrawal is a serious obstacle to self-initiated abstinence, and previous experiences of opioid withdrawal may exacerbate the severity of subsequent incidences.

methodsTo study the impact of repeated opioid withdrawal episodes, we compared male and female mice after one or five cycles of fentanyl exposure and withdrawal. We selectively expressed hemagglutinin-tagged ribosomes (RiboTag) in microglia of transgenic mice to immunoprecipitate and sequence RNA actively undergoing translation (the "translatome") from striatal microglia during fentanyl withdrawal. Key changes were confirmed by RTqPCR of RiboTag RNA.

resultsRepeated bouts of fentanyl treatment and withdrawal impacted striatal microglia much more than a single cycle of fentanyl followed by withdrawal. Multiple withdrawal cycles reduced ramification of microglial processes, suggesting a more reactive cell state, and induced more severe behavioral withdrawal signs in mice. Five cycles of fentanyl exposure and withdrawal increased the expression of gene networks associated with innate immunity signaling. Indeed, 100% of the genes associated with the "microglia core sensome", were upregulated after five cycles of withdrawal.

conclusionsTogether these results suggest that mouse striatal microglia initiate a proinflammatory response following five, but not one, opioid exposure and withdrawal experiences and suggest that drug therapies targeting microglial innate immune responses may mitigate the severe withdrawal associated with repeated opioid tolerance and withdrawal.

Indexed as

Microglia core sensomeRiboTagRNA sequencingStriatum

Identifiers

PMID41634169

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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.