ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
The role of orphan receptor GPR139 in neuropsychiatric behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.Annals of medicine · 2026Pooled it
- Genetic variants associated with longitudinal changes in brain structure across the lifespan.Nature neuroscience · 2022Pooled it
- The GPR139 agonist TAK-041 produces time-dependent alterations to cerebral blood flow and reward system function in patients with schizophrenia: a randomised placebo-controlled trial.Psychopharmacology · 2026Trial
- Tryptamine from wake-active monoaminergic neurons regulates sleep homeostasis.Nature neuroscience · 2026Article
- Advances in drug addiction research usingFrontiers in cell and developmental biology · 2026Review
- Ultra-large virtual screening unveils potent agonists of the neuromodulatory orphan receptor GPR139.Nature communications · 2025Article
- Alcohol use disorder-associated pain: clinical and preclinical evidence.Alcohol (Fayetteville, N.Y.) · 2025Review
- Orphan Receptor GPRC5B Controls Adult Hippocampal Neurogenesis and Affects Retinoic Acid-Mediated Behaviors.Molecular neurobiology · 2025Article
- Homeostatic scaling of dynorphin signaling by a non-canonical opioid receptor.Nature communications · 2025Article
- GPR139, an Ancient Receptor and an Emerging Target for Neuropsychiatric and Behavioral Disorders.Molecular neurobiology · 2025Review
- Surrogate GPR139 Agonists Reverse Short-Term Startle Habituation Impairment in Larval Zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Triggering and modulation of a complex behavior by a single peptidergic command neuron inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches.Current issues in molecular biology · 2024Review
- Exploiting Cell-Based Assays to Accelerate Drug Development for G Protein-Coupled Receptors.International journal of molecular sciences · 2024Review
- Orphan peptide and G protein-coupled receptor signalling in alcohol use disorder.British journal of pharmacology · 2024Review
- GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish.Frontiers in neuroscience · 2024Article
- CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.BMC bioinformatics · 2023Article
- Cryo-EM structures of orphan GPR21 signaling complexes.Nature communications · 2023Article
- Molecular insights into ligand recognition and G protein coupling of the neuromodulatory orphan receptor GPR139.Cell research · 2022Article
- Habenula bibliometrics: Thematic development and research fronts of a resurgent field.Frontiers in integrative neuroscience · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Orphan G protein Coupled Receptors (GPCRs) present attractive targets both for understanding neuropsychiatric diseases and for development of novel therapeutics. GPR139 is an orphan GPCR expressed in select brain circuits involved in controlling movement, motivation and reward. It has been linked to the opioid and dopamine neuromodulatory systems; however, its role in animal behavior and neuropsychiatric processes is poorly understood. Here we present a comprehensive behavioral characterization of a mouse model with a GPR139 null mutation. We show that loss of GPR139 in mice results in delayed onset hyperactivity and prominent neuropsychiatric manifestations including elevated stereotypy, increased anxiety-related traits, delayed acquisition of operant responsiveness, disruption of cued fear conditioning and social interaction deficits. Furthermore, mice lacking GPR139 exhibited complete loss of pre-pulse inhibition and developed spontaneous 'hallucinogenic' head-twitches, altogether suggesting schizophrenia-like symptomatology. Remarkably, a number of these behavioral deficits could be rescued by the administration of μ-opioid and D2 dopamine receptor (D2R) antagonists: naltrexone and haloperidol, respectively, suggesting that loss of neuropsychiatric manifestations in mice lacking GPR139 are driven by opioidergic and dopaminergic hyper-functionality. The inhibitory influence of GPR139 on D2R signaling was confirmed in cell-based functional assays. These observations define the role of GPR139 in controlling behavior and implicate in vivo actions of this receptor in the neuropsychiatric process with schizophrenia-like pathology.
Indexed as
Identifiers
What OpenQuestion holds
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.