ArticleScience signaling2021
β-Arrestin-dependent ERK signaling reduces anxiety-like and conditioned fear-related behaviors in mice.
Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The Mechanism of G Protein-Coupled Receptor Regulation of Ferroptosis in Hepatic Ischemia-Reperfusion Injury.International journal of molecular sciences · 2026Review
- The clinical implication of β-arrestins-mediated signaling in memory and cognition.Molecular and cellular biochemistry · 2025Review
- Chronic Hyponatremia Potentiates Innate Anxiety-Like Behaviors Through the Dysfunction of Monoaminergic Neurons in Mice.Molecular neurobiology · 2025Article
- TRPC4/5 inhibitors: Phase I results and proof of concept studies.European archives of psychiatry and clinical neuroscience · 2025Review
- G protein-coupled receptors: pivotal hubs in gastric cancer malignancy-from multidimensional crosstalk to precision therapeutics.Journal of translational medicine · 2025Review
- Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization.Nature communications · 2024Article
- Review
- Receptor expression and signaling properties in the brain, and structural ligand motifs that contribute to delta opioid receptor agonist-induced seizures.Neuropharmacology · 2023Review
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- Receptors Involved in Mental Disorders and the Use of Clozapine, Chlorpromazine, Olanzapine, and Aripiprazole to Treat Mental Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- ClickArr: a novel, high-throughput assay for evaluating β-arrestin isoform recruitment.Frontiers in pharmacology · 2023Article
- Circular RNA PUM1 performs as a competing endogenous RNA of microRNA-340-5p to mediate DEAD-box helicase 5 to mitigate cerebral ischemia-reperfusion injury.Bioengineered · 2022Article
- Selective δ-Opioid Receptor Agonist, KNT-127, Facilitates Contextual Fear ExtinctionFrontiers in behavioral neuroscience · 2022Article
- Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions.Frontiers in pharmacology · 2022Article
- Role of ARRB1 in prognosis and immunotherapy: A Pan-Cancer analysis.Frontiers in molecular biosciences · 2022Article
- Identification of a Novel Delta Opioid Receptor Agonist Chemotype with Potential Negative Allosteric Modulator Capabilities.Molecules (Basel, Switzerland) · 2021Article
- Evaluation of Kratom Opioid Derivatives as Potential Treatment Option for Alcohol Use Disorder.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) are implicated in the regulation of fear and anxiety. GPCR signaling involves canonical G protein pathways but can also engage downstream kinases and effectors through scaffolding interactions mediated by β-arrestin. Here, we investigated whether β-arrestin signaling regulates anxiety-like and fear-related behavior in mice in response to activation of the GPCR δ-opioid receptor (δOR or DOR). Administration of β-arrestin-biased δOR agonists to male C57BL/6 mice revealed β-arrestin 2-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the dorsal hippocampus and amygdala and β-arrestin 1-dependent activation of ERK1/2 in the nucleus accumbens. In mice, β-arrestin-biased agonist treatment was associated with reduced anxiety-like and fear-related behaviors, with some overlapping and isoform-specific input. In contrast, applying a G protein-biased δOR agonist decreased ERK1/2 activity in all three regions as well as the dorsal striatum and was associated with increased fear-related behavior without effects on baseline anxiety. Our results indicate a complex picture of δOR neuromodulation in which β-arrestin 1- and 2-dependent ERK signaling in specific brain subregions suppresses behaviors associated with anxiety and fear and opposes the effects of G protein-biased signaling. Overall, our findings highlight the importance of noncanonical β-arrestin-dependent GPCR signaling in the regulation of these interrelated emotions.
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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.