ArticleeNeuro
GPR88 in A2AR Neurons Enhances Anxiety-Like Behaviors.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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
31 citing papers in PubMed, 39 citations in OpenAlex.
- GPR88 localization to primary cilia in neurons is cell-type specific.Life science alliance · 2026Article
- Identifying disease progression biomarkers in metabolic associated steatotic liver disease (MASLD) through weighted gene co-expression network analysis and machine learning.Journal of translational medicine · 2025Article
- Genetic and Environmental Influences on Anxiety Disorders: A Systematic Review of Their Onset and Development.Cureus · 2025Review
- The GPR88 Agonist RTI-122 Reduces Alcohol-Related Motivation and Consumption.Addiction biology · 2025Article
- GPR88 promotes neurite outgrowth of sensory neurons via activation of GFrontiers in pharmacology · 2025Article
- Orphan peptide and G protein-coupled receptor signalling in alcohol use disorder.British journal of pharmacology · 2024Review
- Improvement of the Metabolic Stability of GPR88 Agonist RTI-13951-33: Design, Synthesis, and Biological Evaluation.Journal of medicinal chemistry · 2023Article
- Synthesis and pharmacological validation of a novel radioligand for the orphan GPR88 receptor.Bioorganic & medicinal chemistry letters · 2023Article
- Chronic tianeptine induces tolerance in analgesia and hyperlocomotion via mu-opioid receptor activation in mice.Frontiers in psychiatry · 2023Article
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion ofFrontiers in physiology · 2022Article
- Evaluation of Amide Bioisosteres Leading to 1,2,3-Triazole Containing Compounds as GPR88 Agonists: Design, Synthesis, and Structure-Activity Relationship Studies.Journal of medicinal chemistry · 2021Article
- Design, Synthesis, and Structure-Activity Relationship Studies of (4-Alkoxyphenyl)glycinamides and Bioisosteric 1,3,4-Oxadiazoles as GPR88 Agonists.Journal of medicinal chemistry · 2020Article
- Review
- The orphan receptor GPR88 blunts the signaling of opioid receptors and multiple striatal GPCRs.eLife · 2020Article
- Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.Science (New York, N.Y.) · 2019Article
- Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target.ACS chemical neuroscience · 2019Review
- Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home cage phenotyping.Genes, brain, and behavior · 2018Article
- Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake.Journal of medicinal chemistry · 2018Article
- Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice.Biology of reproduction · 2018Article
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 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GPR88 is an orphan G-protein-coupled receptor highly expressed in striatal dopamine D1 (receptor) R- and D2R-expressing medium spiny neurons. This receptor is involved in activity and motor responses, and we previously showed that this receptor also regulates anxiety-like behaviors. To determine whether GPR88 in D2R-expressing neurons contributes to this emotional phenotype, we generated conditional Gpr88 knock-out mice using adenosine A2AR (A2AR)-Cre-driven recombination, and compared anxiety-related responses in both total and A2AR-Gpr88 KO mice. A2AR-Gpr88 KO mice showed a selective reduction of Gpr88 mRNA in D2R-expressing, but not D1R-expressing, neurons. These mutant mice showed increased locomotor activity and decreased anxiety-like behaviors in light/dark and elevated plus maze tests. These phenotypes were superimposable on those observed in total Gpr88 KO mice, demonstrating that the previously reported anxiogenic activity of GPR88 operates at the level of A2AR-expressing neurons. Further, A2AR-Gpr88 KO mice showed no change in novelty preference and novelty-suppressed feeding, while these responses were increased and decreased, respectively, in the total Gpr88 KO mice. Also, A2AR-Gpr88 KO mice showed intact fear conditioning, while the fear responses were decreased in total Gpr88 KO. We therefore also show for the first time that GPR88 activity regulates approach behaviors and conditional fear; however, these behaviors do not seem mediated by receptors in A2AR neurons. We conclude that Gpr88 expressed in A2AR neurons enhances ethological anxiety-like behaviors without affecting conflict anxiety and fear responses.
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.