ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Morphine induces AMPA receptor internalization in primary hippocampal neurons via calcineurin-dependent dephosphorylation of GluR1 subunits.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer's disease.Translational neurodegeneration · 2023Article
- Kappa opioid receptor modulation of excitatory drive onto nucleus accumbens fast-spiking interneurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Phosphorylation in two discrete tau domains regulates a stepwise process leading to postsynaptic dysfunction.The Journal of physiology · 2021Article
- PKC and Ras are Involved in M1 Muscarinic Receptor-Mediated Modulation of AMPA Receptor GluA1 Subunit.Cellular and molecular neurobiology · 2020Article
- C2-lacking isoform of Nedd4-2 regulates excitatory synaptic strength through GluA1 ubiquitination-independent mechanisms.Journal of neurochemistry · 2019Article
- Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.Nature reviews. Neuroscience · 2019Review
- Perampanel Affects Up-Stream Regulatory Signaling Pathways of GluA1 Phosphorylation in Normal and Epileptic Rats.Frontiers in cellular neuroscience · 2019Article
- A53T Mutant Alpha-Synuclein Induces Tau-Dependent Postsynaptic Impairment Independently of Neurodegenerative Changes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Cyclosporin A attenuating morphine tolerance through inhibiting NO/ERK signaling pathway in human glioblastoma cell line: the involvement of calcineurin.EXCLI journal · 2018Article
- Inhibition of Calcineurin A by FK506 Suppresses Seizures and Reduces the Expression of GluN2B in Membrane Fraction.Neurochemical research · 2017Article
- Reduced cortical excitatory synapse number in APOE4 mice is associated with increased calcineurin activity.Neuroreport · 2017Article
- Neonatal Maternal Deprivation Enhances Presynaptic P2X7 Receptor Transmission in Insular Cortex in an Adult Rat Model of Visceral Hypersensitivity.CNS neuroscience & therapeutics · 2017Article
- Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses.Nature neuroscience · 2016Article
- Naltrexone Facilitates Learning and Delays Extinction by Increasing AMPA Receptor Phosphorylation and Membrane Insertion.Biological psychiatry · 2016Article
- Insular Cortex is Critical for the Perception, Modulation, and Chronification of Pain.Neuroscience bulletin · 2016Review
- A Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer's Disease.Frontiers in aging neuroscience · 2016Article
- Phosphorylation of the N-methyl-d-aspartate receptor is increased in the nucleus accumbens during both acute and extended morphine withdrawal.The Journal of pharmacology and experimental therapeutics · 2015Article
- GluA1 phosphorylation contributes to postsynaptic amplification of neuropathic pain in the insular cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.Molecular brain · 2014Article
- Tau phosphorylation and tau mislocalization mediate soluble Aβ oligomer-induced AMPA glutamate receptor signaling deficits.The European journal of neuroscience · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic morphine treatment resulting in the alteration of postsynaptic levels of AMPA receptors, thereby modulating synaptic strength, has been reported. However, the mechanism underlying such drug-induced synaptic modification has not been resolved. By monitoring the GluR1 trafficking in primary hippocampal neurons using the pHluorin-GluR1 imaging and biotinylation studies, we observed that prolonged morphine exposure significantly induced loss of synaptic and extrasynaptic GluR1 by internalization. The morphine-induced GluR1 endocytosis was independent of neural network activities or NMDA receptor activities, as neither blocking the sodium channels with tetrodotoxin nor NMDA receptors with dl-APV altered the effects of morphine. Instead, morphine-induced GluR1 endocytosis is attributed to a change in the phosphorylation state of the GluR1 at Ser(845) as morphine significantly decreased the dephosphorylation of GluR1 at this site. Such changes in Ser(845) phosphorylation required morphine-induced activation of calcineurin, based on the observations that a calcineurin inhibitor, FK506, completely abrogated the dephosphorylation, and morphine treatment led to an increase in calcineurin enzymatic activity, even in the presence of dl-APV. Importantly, pretreatment with FK506 and overexpression of the GluR1 mutants, S845D (phospho-mimic) or S845A (phospho-blocking) attenuated the morphine-induced GluR1 endocytosis. Therefore, the calcineurin-mediated GluR1-S845 dephosphorylation is critical for the morphine-induced changes in the postsynaptic AMPA receptor level. Together, these findings reveal a novel molecular mechanism for opioid-induced neuronal adaptation and/or synaptic impairment.
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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.