ArticleBiological psychiatry global open science2022
A cAMP-Related Gene Network in Microglia Is Inversely Regulated by Morphine Tolerance and Withdrawal.
Article in Biological psychiatry global open science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- Repeated fentanyl abstinence intensifies opioid withdrawal and induces a proinflammatory state in striatal microglia.Psychopharmacology · 2026Article
- Regulation of glial markers expression in the rat basolateral amygdala and hippocampus during morphine aversive memory retrieval and its extinction.Behavioral and brain functions : BBF · 2025Article
- Repeated fentanyl abstinence intensifies opioid withdrawal and induces a proinflammatory state in striatal microglia.bioRxiv : the preprint server for biology · 2025Article
- Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond.Journal of neuroimmunology · 2025Review
- Review
- Transcriptional signatures of fentanyl use in the mouse ventral tegmental area.Addiction biology · 2024Article
- Article
- Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.Nature communications · 2024Article
- Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study.Frontiers in microbiology · 2024Article
- A unique role for cAMP signaling in microglia during opioid tolerance and withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Transcriptional and epigenetic regulation of microglia in substance use disorders.Molecular and cellular neurosciences · 2023Review
- Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice.Frontiers in behavioral neuroscience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Background: Microglia have recently been implicated in opioid dependence and withdrawal. Mu Opioid (MOR) receptors are expressed in microglia, and microglia form intimate connections with nearby neurons. Accordingly, opioids have both direct (MOR mediated) and indirect (neuron-interaction mediated) effects on microglia function. Methods: To investigate this directly, we used RNA sequencing of ribosome-associated RNAs from striatal microglia (RiboTag-Seq) after the induction of morphine tolerance and followed by naloxone precipitated withdrawal (n=16). We validated the RNA-Seq data by combining fluorescent in-situ hybridization with immunohistochemistry for microglia (n=18). Finally, we expressed and activated the Gi/o-coupled hM Results: We detected large, inverse changes in RNA translation following opioid tolerance and withdrawal. WGCNA analysis revealed an intriguing network of cAMP-associated genes that are known to be involved in microglial motility, morphology, and interactions with neurons that were downregulated with morphine tolerance and upregulated rapidly by withdrawal. Three-dimensional histological reconstruction of microglia allowed for volumetric, visual colocalization of mRNA within individual microglia that validated our bioinformatics results. Direct activation of Gi/o-coupled DREADD receptors in CX3CR1-expressing cells exacerbated signs of opioid withdrawal rather than mimicking the effects of morphine. Conclusions: These results indicate that Gi-signaling and cAMP-associated gene networks are inversely engaged during opioid tolerance and early withdrawal, perhaps revealing a role of microglia in mitigating the consequences of opioids.
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Registered trials
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.