ArticleFrontiers in neuroscience2016
BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone.
Article in Frontiers in neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Where do we stand on fMRI in awake mice?Cerebral cortex (New York, N.Y. : 1991) · 2024Pooled it
- Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead.Neuroscience and biobehavioral reviews · 2019Pooled it
- Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Opioid-specific brain connectivity dynamics distinguish analgesia from secondary effects: Studies in male mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats.Frontiers in neuroscience · 2025Article
- High-resolution awake mouse fMRI at 14 Tesla.bioRxiv : the preprint server for biology · 2024Article
- Palmitoylethanolamide causes dose-dependent changes in brain function and the lipidome.Frontiers in neuroscience · 2024Article
- Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: brain oxygen level-dependent fMRI study in awake rats.Brain communications · 2024Article
- Neuroimaging of opioid exposure: a review of preclinical animal models to inform addiction research.Psychopharmacology · 2023Review
- Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments.Pharmacological reviews · 2023Review
- Putative neurochemical and cell type contributions to hemodynamic activity in the rodent caudate putamen.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Connectomic analysis of Alzheimer's disease using percolation theory.Network neuroscience (Cambridge, Mass.) · 2022Article
- Male and Female C57BL/6 Mice Respond Differently to Awake Magnetic Resonance Imaging Habituation.Frontiers in neuroscience · 2022Article
- Applications in Awake Animal Magnetic Resonance Imaging.Frontiers in neuroscience · 2022Review
- The utility of maraviroc, an antiretroviral agent used to treat HIV, as treatment for opioid abuse? Data from MRI and behavioural testing in rats.Journal of psychiatry & neuroscience : JPN · 2021Article
- Oxycodone in the Opioid Epidemic: High 'Liking', 'Wanting', and Abuse Liability.Cellular and molecular neurobiology · 2021Review
- Cannabidiol has a unique effect on global brain activity: a pharmacological, functional MRI study in awake mice.Journal of translational medicine · 2021Article
- Recent advances in basic science methodology to evaluate opioid safety profiles and to understand opioid activities.Faculty reviews · 2021Review
- Progress in opioid reward research: From a canonical two-neuron hypothesis to two neural circuits.Pharmacology, biochemistry, and behavior · 2021Review
- Evolution of brain-wide activity in the awake behaving mouse after acute fear by longitudinal manganese-enhanced MRI.NeuroImage · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high μ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala, and hypothalamus), and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex, and prelimbic cortex). Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala, and preoptic areas). This result indicates that most effects of OXY on positive BOLD are mediated by the μ opioid receptor (on-target effects). OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122) and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum), and in some case intensified (hippocampus). Negative BOLD analysis therefore shows activation and deactivation events in the absence of the μ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects). Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY brain signature that should, in the future, be compared to other μ opioid agonists.
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