ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Receptor Reserve Moderates Mesolimbic Responses to Opioids in a Humanized Mouse Model of the OPRM1 A118G Polymorphism.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Low μ-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Neural Network Connectivity Following Opioid Dependence is Altered by a Common Genetic Variant in the µ-Opioid Receptor,The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Opioid trail: Tracking contributions to opioid use disorder from host genetics to the gut microbiome.Neuroscience and biobehavioral reviews · 2024Review
- The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder.Neuropharmacology · 2023Review
- Translational Research in Nicotine Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.Molecular psychiatry · 2020Article
- Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment.Neuroscience and biobehavioral reviews · 2019Review
- Synaptic Regulation by OPRM1 Variants in Reward Neurocircuitry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.Frontiers in psychiatry · 2019Review
- Opioid receptors: drivers to addiction?Nature reviews. Neuroscience · 2018Review
- Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src.Scientific reports · 2017Article
- Convergent Balancing Selection on the Mu-Opioid Receptor in Primates.Molecular biology and evolution · 2017Article
- Genetic variation in the behavioral effects of buprenorphine in female mice derived from a murine model of the OPRM1 A118G polymorphism.Neuropharmacology · 2017Article
- Morphine-induced antinociception and reward in "humanized" mice expressing the mu opioid receptor A118G polymorphism.Brain research bulletin · 2016Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The OPRM1 A118G polymorphism is the most widely studied μ-opioid receptor (MOR) variant. Although its involvement in acute alcohol effects is well characterized, less is known about the extent to which it alters responses to opioids. Prior work has shown that both electrophysiological and analgesic responses to morphine but not to fentanyl are moderated by OPRM1 A118G variation, but the mechanism behind this dissociation is not known. Here we found that humanized mice carrying the 118GG allele (h/mOPRM1-118GG) were less sensitive than h/mOPRM1-118AA littermates to the rewarding effects of morphine and hydrocodone but not those of other opioids measured with intracranial self-stimulation. Reduced morphine reward in 118GG mice was associated with decreased dopamine release in the nucleus accumbens and reduced effects on GABA release in the ventral tegmental area that were not due to changes in drug potency or efficacy in vitro or receptor-binding affinity. Fewer MOR-binding sites were observed in h/mOPRM1-118GG mice, and pharmacological reduction of MOR availability unmasked genotypic differences in fentanyl sensitivity. These findings suggest that the OPRM1 A118G polymorphism decreases sensitivity to low-potency agonists by decreasing receptor reserve without significantly altering receptor function.
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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.