ArticleMolecular psychiatry2020
Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.Journal of clinical laboratory analysis · 2022Pooled it
- Spatial transcriptomics reveals distinct cell type dynamics following opioid dependence in female mice with the common human μ-opioid receptor variant Oprm1 A118G.Nature communications · 2026Article
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- Mutations of schizophrenia risk gene SETD1A dysregulate synaptic function in human neurons.Molecular psychiatry · 2025Article
- Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.Science advances · 2024Article
- Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs.Stem cell reports · 2024Article
- Receptor Pharmacogenomics: Deciphering Genetic Influence on Drug Response.International journal of molecular sciences · 2024Review
- Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.Molecular psychiatry · 2024Article
- Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Scaled and Efficient Derivation of Loss of Function Alleles in Risk Genes for Neurodevelopmental and Psychiatric Disorders in Human iPSC.bioRxiv : the preprint server for biology · 2024Article
- Comparing stem cells, transdifferentiation and brain organoids as tools for psychiatric research.Translational psychiatry · 2024Review
- Postmortem-derived iPSC models in substance use disorders research.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology.Frontiers in cellular neuroscience · 2024Review
- 5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.Genes, brain, and behavior · 2023Review
- Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.Molecular psychiatry · 2023Article
- A human stem cell-derived neuronal model of morphine exposure reflects brain dysregulation in opioid use disorder: Transcriptomic and epigenetic characterization of postmortem-derived iPSC neurons.Frontiers in psychiatry · 2023Article
- Methods for shipping live primary cortical and hippocampal neuron cultures from postnatal mice.Current research in neurobiology · 2023Review
- Whole Cell Patch Clamp Electrophysiology in Human Neuronal Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- On the utilization of the induced pluripotent stem cell (iPSC) model to study substance use disorders: A scoping review protocol.PloS one · 2023Article
- Optimized splitting of mixed-species RNA sequencing data.Journal of bioinformatics and computational biology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown. The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans. With opioid abuse-related deaths rising at unprecedented rates, understanding these mechanisms may provide a path to therapy. Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission. We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects. To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs. In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D. This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
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