ArticleBMC neuroscience2018
Chronic oxycodone induces axonal degeneration in rat brain.
Article in BMC neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Spontaneous oxycodone withdrawal alters behavior and oligodendrocyte-related gene expression in mice.Pharmacology, biochemistry, and behavior · 2026Article
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- Neurorestorative properties of ibogaine: linking multi-receptor affinities to remyelination and metabolic restoration.Acta neuropsychiatrica · 2026Review
- Prenatal fentanyl exposure affects social dominance and myelination patterns in the adult mouse brain.Neuropharmacology · 2025Article
- The Rise of Fentanyl: Molecular Aspects and Forensic Investigations.International journal of molecular sciences · 2025Review
- Frontal White Matter Changes and Craving Recovery in Inpatients With Heroin Use Disorder.JAMA network open · 2024Article
- Mild Encephalopathy/Encephalitis with Reversible Splenial Lesions after Amphetamine and Opioid Use.Internal medicine (Tokyo, Japan) · 2024Article
- Article
- LY2940094, an NOPR antagonist, promotes oligodendrocyte generation and myelin recovery in an NOPR independent manner.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- FRONTAL WHITE MATTER CHANGES INDICATE RECOVERY WITH INPATIENT TREATMENT IN HEROIN ADDICTION.medRxiv : the preprint server for health sciences · 2024Article
- Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Article
- Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use.International journal of molecular sciences · 2023Article
- Novel RNA-Seq Signatures Post-Methamphetamine and Oxycodone Use in a Model of HIV-Associated Neurocognitive Disorders.Viruses · 2023Article
- Neuroimmune Mechanisms of Opioid Use Disorder and Recovery: Translatability to Human Studies, and Future Research Directions.Neuroscience · 2023Review
- P2Y1 receptor in the colonic submucosa of rats and its association with opioid‑induced constipation.Experimental and therapeutic medicine · 2023Article
- Can Essential Oils Provide an Alternative Adjuvant Therapy for COVID-19 Infections and Pain Management at the Same Time?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure.Cells · 2022Article
- Effects of fentanyl on acute locomotor activity, behavioral sensitization, and contextual reward in female and male rats.Drug and alcohol dependence · 2021Article
- Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.Cellular and molecular neurobiology · 2021Article
- Transcriptional Alterations in Dorsolateral Prefrontal Cortex and Nucleus Accumbens Implicate Neuroinflammation and Synaptic Remodeling in Opioid Use Disorder.Biological psychiatry · 2021Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundChronic opioid therapy for non-malignant pain conditions has significantly increased over the last 15 years. Recently, the correlation between opioid analgesics and alternations in brain structure, such as leukoencephalopathy, axon demyelination, and white matter lesions, has been demonstrated in patients with a history of long-term use of prescription opioids. The exact mechanisms underlying the neurotoxic effect of opioids on the central nervous system are still not fully understood. We investigated the effect of chronic opioids using an animal model in which female rats were orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days. In addition we tested oxycodone, morphine and DAMGO in breast adenocarcinoma MCF7 cells, which are known to express the μ-opioid receptor.
resultsWe observed several changes in the white matter of animals treated with oxycodone: deformation of axonal tracks, reduction in size of axonal fascicles, loss of myelin basic protein and accumulation of amyloid precursor protein beta (β-APP), suggesting axonal damages by chronic oxycodone. Moreover, we demonstrated activation of pro-apoptotic machinery amid suppression of anti-apoptotic signaling in axonal tracks that correlated with activation of biomarkers of the integrated stress response (ISR) in these structures after oxycodone exposure. Using MCF7 cells, we observed induction of the ISR and pro-apoptotic signaling after opioid treatment. We showed that the ISR inhibitor, ISRIB, suppresses opioid-induced Bax and CHOP expression in MCF7 cells.
conclusionsAltogether, our data suggest that chronic opioid administration may cause neuronal degeneration by activation of the integrated stress response leading to induction of apoptotic signaling in neurons and also by promoting demyelination in CNS.
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