ArticleBiological psychiatry2010
Brain region specific actions of regulator of G protein signaling 4 oppose morphine reward and dependence but promote analgesia.
Article in Biological psychiatry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Identification of a Novel Population of Neuromedin S Expressing Neurons in the Ventral Tegmental Area That Promote Morphine-Elicited Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Reduced striatal M4-cholinergic signaling following dopamine loss contributes to parkinsonian and l-DOPA-induced dyskinetic behaviors.Science advances · 2024Article
- Genetic mouse models in opioid research: current status and future directions.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- RGS4 Actions in Mouse Prefrontal Cortex Modulate Behavioral and Transcriptomic Responses to Chronic Stress and Ketamine.Molecular pharmacology · 2024Article
- Changes in Plasma Metabolic Signature upon Acute and Chronic Morphine Administration in Morphine-Tolerant Mice.Metabolites · 2023Article
- βγ G-proteins, but not regulators of G-protein signaling 4, modulate opioid-induced respiratory rate depression.Frontiers in physiology · 2023Article
- A Regional and Projection-Specific Role of RGSz1 in the Ventrolateral Periaqueductal Grey in the Modulation of Morphine Reward.Molecular pharmacology · 2023Article
- A peptide blocking the ADORA1-neurabin interaction is anticonvulsant and inhibits epilepsy in an Alzheimer's model.JCI insight · 2022Article
- Glutamatergic Systems and Memory Mechanisms Underlying Opioid Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Regulators of G Protein Signaling in Analgesia and Addiction.Molecular pharmacology · 2020Review
- Article
- Regulator of G-Protein Signaling (RGS) Protein Modulation of Opioid Receptor Signaling as a Potential Target for Pain Management.Frontiers in molecular neuroscience · 2020Review
- Identification of Dysregulated Genes for Late-Onset Alzheimer's Disease Using Gene Expression Data in Brain.Journal of Alzheimer's disease & Parkinsonism · 2020Article
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- The Opioid Crisis and the Future of Addiction and Pain Therapeutics.The Journal of pharmacology and experimental therapeutics · 2019Review
- RGS4 Maintains Chronic Pain Symptoms in Rodent Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Role of RGS12 in the differential regulation of kappa opioid receptor-dependent signaling and behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Regulators of G-Protein Signaling (RGS) Proteins Promote Receptor Coupling to G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Regulator of G-Protein Signaling 4 (RGS4) Controls Morphine Reward by Glutamate Receptor Activation in the Nucleus Accumbens of Mouse Brain.Molecules and cells · 2018Article
- Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundRegulator of G protein signaling 4 (RGS4) is one of the smaller members of the RGS family of proteins, which are known to control signaling amplitude and duration via interactions with G protein alpha subunits or other signaling molecules. Earlier evidence suggests dynamic regulation of RGS4 levels in neuronal networks mediating actions of opiates and other drugs of abuse, but the consequences of RGS4 actions in vivo are largely unknown.
methodsIn this study, we use constitutive and nucleus accumbens-inducible RGS4 knockout mice as well as mice overexpressing RGS4 in the nucleus accumbens via viral mediated gene transfer, to examine the influence of RGS4 on behavioral responses to opiates. We also use electrophysiology and immunoprecipitation assays to further understand the mechanisms underlying the tissue-specific actions of RGS4.
resultsInducible knockout or selective overexpression of RGS4 in the nucleus accumbens reveals that, in this brain region, RGS4 acts as a negative regulator of morphine reward, whereas in the locus coeruleus RGS4 opposes morphine physical dependence. In contrast, we show that RGS4 does not affect morphine analgesia or tolerance but is a positive modulator of certain opiate analgesics, such as methadone and fentanyl.
conclusionsThese findings provide fundamentally novel information concerning the role of RGS4 in the cellular mechanisms underlying the diverse actions of opiate drugs in the nervous system.
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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.