Affinage

GRM8

Metabotropic glutamate receptor 8 · UniProt O00222

Length
908 aa
Mass
101.7 kDa
Annotated
2026-04-28
59 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRM8 encodes metabotropic glutamate receptor 8 (mGluR8), a presynaptic group III metabotropic glutamate receptor that functions as a key negative regulator of neurotransmitter release across diverse brain circuits including the hippocampal lateral perforant path, amygdala, bed nucleus of the stria terminalis, superior colliculus, olfactory-piriform pathway, retina, and thalamocortical circuits (PMID:8710211, PMID:12213276, PMID:16188284, PMID:21451497, PMID:38918065). Receptor activation, initiated by closure of its extracellular Venus flytrap module whose structural basis has been resolved by X-ray crystallography (PMID:12151600, PMID:29402739, PMID:30365309), couples through pertussis toxin-sensitive Gi/o proteins via Gβγ subunits to suppress vesicle fusion not by blocking presynaptic Ca²⁺ entry but by reducing the apparent Ca²⁺ affinity of the release sensor (PMID:15623786, PMID:21903594). mGluR8 modulates both glutamatergic and GABAergic transmission, and its genetic ablation produces increased anxiety, disrupted sensorimotor gating, and altered fear conditioning, establishing roles in stress-related and sensory processing circuitry (PMID:12213279, PMID:21451497, PMID:23664812, PMID:38918065).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 High

    Establishing that mGluR8 is a presynaptic receptor resolved the question of where this receptor acts within neural circuits, placing it at axon terminals of projection neurons where it could modulate neurotransmitter release.

    Evidence Immunohistochemistry with EM and lateral olfactory tract transection in rat olfactory bulb

    PMID:8710211

    Open questions at the time
    • Mechanism of presynaptic inhibition not yet identified
    • Distribution beyond olfactory bulb not yet mapped
  2. 1998 High

    Characterizing two splice variants (mGluR8a/8b) with identical pharmacological profiles and demonstrating Gi/o-coupled signaling established the receptor's G-protein coupling and pharmacological identity.

    Evidence Heterologous expression in HEK293 cells and Xenopus oocytes with pharmacological profiling and Kir3 channel coupling

    PMID:9875342

    Open questions at the time
    • Native G-protein coupling pathway in neurons not yet confirmed
    • Functional difference between splice variants unknown
  3. 2002 High

    Mutagenesis of Venus flytrap module residues that converted antagonists to agonists established that closure of this extracellular domain is the activation switch, and knockout studies defined pathway-specific autoreceptor function at hippocampal lateral perforant path synapses.

    Evidence Site-directed mutagenesis with functional assays; electrophysiology in hippocampal slices from wild-type vs. mGluR8 knockout mice with selective agonist DCPG

    PMID:12151600 PMID:12213276

    Open questions at the time
    • Crystal structure of the ATD not yet solved
    • Downstream signaling mechanism at native synapses unknown
  4. 2002 Medium

    Demonstrating that mGluR8 knockout mice exhibit increased anxiety established a behavioral role for the receptor in modulating stress responses, motivating circuit-level investigation.

    Evidence Elevated plus maze behavioral phenotyping in mGluR8 knockout mice

    PMID:12213279

    Open questions at the time
    • Brain region(s) mediating the anxiogenic phenotype not identified
    • Single behavioral paradigm in one lab
  5. 2005 High

    Identification of Gβγ as the effector subunit mediating mGluR8's modulation of Ca²⁺ influx, and demonstration that mGluR8 presynaptically inhibits sensory transmission in the lateral amygdala to suppress fear-potentiated startle, defined both the proximal signaling mechanism and a fear-circuit function.

    Evidence Microspectrofluorimetry in rod photoreceptors with pertussis toxin, suramin, and Gβγ-inhibiting peptide; patch-clamp in amygdala slices plus in vivo fear-potentiated startle with intra-amygdala DCPG

    PMID:15623786 PMID:16188284

    Open questions at the time
    • Whether Gβγ acts on channels or release machinery not distinguished
    • Downstream effector in amygdala neurons not identified
  6. 2010 Medium

    Showing that mGluR8 suppresses both excitatory and inhibitory synaptic conductances in the retina extended the receptor's role to sensory processing circuits and demonstrated regulation of both glutamate and GABA release.

    Evidence Light-evoked recordings in wild-type and mGluR8-deficient mouse retinas

    PMID:20096339

    Open questions at the time
    • Specific cell types expressing mGluR8 in retina not fully resolved
    • Single lab
  7. 2011 High

    Demonstrating that mGluR8 suppresses release without affecting presynaptic Ca²⁺ entry but instead by reducing Ca²⁺ affinity of the vesicle release sensor resolved a long-standing question about how group III mGluRs inhibit transmission, revealing a novel mechanism acting downstream of Ca²⁺ influx.

    Evidence Presynaptic Ca²⁺ imaging combined with miniature EPSC recording and quantitative modeling at hippocampal lateral perforant path synapses

    PMID:21903594

    Open questions at the time
    • Molecular identity of the release sensor target unknown
    • Whether this mechanism generalizes to all mGluR8-expressing synapses not tested
  8. 2011 High

    Discovery that stress and noradrenergic signaling disrupt mGluR8-mediated presynaptic inhibition in the BNST linked receptor function to stress-circuit plasticity.

    Evidence Electrophysiology in BNST slices from wild-type and mGluR8 KO mice with α1 adrenergic pharmacology and acute/chronic restraint stress

    PMID:21451497

    Open questions at the time
    • Molecular mechanism of adrenergic cross-talk with mGluR8 signaling not defined
    • Whether stress-induced mGluR8 dysfunction contributes to anxiety phenotype unclear
  9. 2018 High

    Crystal structures of the human mGluR8 ATD bound to L-AP4, L-glutamate, and DCPG provided the first atomic-resolution view of ligand recognition and explained the structural basis for subtype selectivity.

    Evidence X-ray crystallography of recombinant human mGlu8 ATD with multiple ligands and comparative structural analysis

    PMID:29402739 PMID:30365309

    Open questions at the time
    • Full-length receptor structure not available
    • Active-state conformational transitions not captured
  10. 2024 High

    Cell-type-specific deletion in parvalbumin-expressing thalamic reticular nucleus neurons revealed that mGluR8 gates excitatory drive onto dorsal thalamus relay cells and controls sensorimotor gating, establishing a thalamocortical circuit function.

    Evidence Conditional PV-Cre knockout, AAV-mediated TRN knockdown, ex vivo electrophysiology, prepulse inhibition and locomotor behavioral testing

    PMID:38918065

    Open questions at the time
    • Downstream signaling in TRN neurons not characterized
    • Whether TRN mGluR8 loss contributes to psychiatric disease phenotypes not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of the vesicle release sensor targeted by mGluR8 signaling and the full-length receptor structure in active and inactive conformations remain unknown.
  • No identification of the release machinery component whose Ca²⁺ affinity is reduced
  • No full-length cryo-EM or crystal structure
  • Mechanism of noradrenergic/stress-induced disruption of mGluR8 signaling not molecularly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-162582 Signal Transduction 3
Partners
GNAI1GNB1TRPA1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 mGluR8 is localized presynaptically in axon terminals of projection neurons of the main olfactory bulb; immunoreactivity was reduced after lateral olfactory tract transection and was found in axon terminals making asymmetric synapses with dendritic spines. Immunohistochemistry with specific anti-mGluR8 antibody, axonal lesion (lateral olfactory tract transection), light and electron microscopy Neuroscience letters High 8710211
1998 mGluR8a and mGluR8b splice variants, differing in their C-terminal domains, exhibit identical pharmacological profiles (rank order: DL-AP4 > L-serine-O-phosphate > glutamate) when expressed in HEK293 cells coupled to chimeric Gαqi9, and mGluR8 mediates glutamate-induced currents in Xenopus oocytes coexpressing Kir3.1/3.4 that are antagonized by the group II/III antagonist CPPG. Heterologous expression in HEK293 cells and Xenopus oocytes, pharmacological profiling, electrophysiology The European journal of neuroscience High 9875342
2002 Closure of the Venus flytrap module (VFTM) of the mGluR8 extracellular domain is required for receptor activation; antagonists ACPT-II and MAP4 prevent VFTM closure through ionic (Asp-309) and steric (Tyr-227) hindrance, and mutation of these residues to Ala converts them into full agonists. Molecular modeling, site-directed mutagenesis of active-site residues, functional assay in heterologous expression system Proceedings of the National Academy of Sciences of the United States of America High 12151600
2002 mGluR8 functions as a presynaptic autoreceptor on lateral perforant path (LPP) afferents to the dentate gyrus; selective agonist DCPG and L-AP4 suppress LPP-evoked fEPSPs in wild-type slices but not in mGluR8 knockout slices, while medial perforant path fEPSPs are unaffected. Electrophysiological field recording in hippocampal slices from wild-type and mGluR8 knockout mice Neuropharmacology High 12213276
2002 mGluR8 deficiency in mice leads to increased anxiety-related behavior (elevated plus maze), demonstrating a role for the receptor in modulating responses to novel stressful environments without affecting locomotor activity. mGluR8 knockout mouse behavioral phenotyping (elevated plus maze) Neuropharmacology Medium 12213279
2002 mGluR8 receptor activation reduces excitatory synaptic transmission in the superficial superior colliculus via presynaptic mechanisms in the retino-collicular pathway; DCPG (EC50 ~1.25 μM) reduces optic tract-evoked fEPSPs, an effect antagonized by LY341495 at concentrations selective for mGluR8. In vitro field EPSP recording in rat superior colliculus slices with selective pharmacology Neuropharmacology Medium 12213277
2003 Systemic administration of the mGluR8 agonist (S)-3,4-DCPG induces c-Fos in stress-related brain regions (paraventricular hypothalamus, central amygdala, locus coeruleus, lateral parabrachial nucleus) in wild-type but not mGluR8 knockout mice; over 92% of c-Fos-positive neurons in the central amygdala were GABAergic. c-Fos immunohistochemistry, mGluR8 knockout mice, cell-type identification Neuropharmacology High 12907308
2005 mGluR8 activation in the periaqueductal grey (PAG) via (S)-3,4-DCPG increases extracellular glutamate and decreases GABA; both effects require coupling to adenylate cyclase and subsequent PKA activation, as the PKA inhibitor H-89 abolishes these changes. In vivo microdialysis in rat PAG, pharmacological inhibition of PKA (H-89) and adenylate cyclase, selective group III antagonists Neuropharmacology Medium 16084932
2005 mGluR8 activation by (S)-3,4-DCPG in the lateral amygdala acts presynaptically to reduce synaptic transmission from sensory afferents (shown by lack of postsynaptic effects and altered short-term plasticity in patch clamp), and inhibits both acquisition and expression of fear-potentiated startle in vivo. Patch-clamp electrophysiology in rat brain slices, in vivo fear-potentiated startle, intra-amygdala drug injection Neuropharmacology High 16188284
2005 mGluR8 in photoreceptors modulates cytosolic Ca2+ concentration by inhibiting extracellular Ca2+ influx via a pertussis toxin-sensitive G protein (Gi/o) acting through the Gβγ subunit; suramin, pertussis toxin, and a Gβγ-inhibiting peptide all abolish this effect, while cholera toxin (Gs activator) does not. Microspectrofluorimetry of Ca2+ in acutely isolated rod photoreceptors, pharmacological G-protein dissection (pertussis toxin, cholera toxin, suramin, Gβγ-inhibiting peptide) Investigative ophthalmology & visual science High 15623786
2008 Both mGluR4 and mGluR8 mediate presynaptic inhibition of excitatory transmission at the lateral olfactory tract-piriform cortex synapse; the selective mGluR8 agonist DCPG (300 nM) suppresses synaptic transmission, and the mGluR4 positive allosteric modulator PHCCC potentiates L-AP4 effects at this synapse. Whole-cell patch-clamp recording in piriform cortex pyramidal cells, selective agonists/modulators Neuropharmacology Medium 18625254
2011 mGluR8 inhibits glutamate release in hippocampal lateral perforant path synapses without affecting presynaptic Ca2+ entry, diffusion, or buffering; instead it decreases the apparent Ca2+ affinity of the vesicle release sensor and reduces maximal release rate, consistent with a direct effect on the release machinery that is resistant to adenylate cyclase inhibition. Presynaptic Ca2+ imaging, miniature EPSC recording, quantitative modeling of Ca2+ dependence, pharmacological blockade of classical G-protein pathways Cerebral cortex High 21903594
2011 mGluR8 mediates presynaptic suppression of excitatory transmission in the bed nucleus of the stria terminalis (BNST); this effect is absent in mGluR8 KO mice, is associated with increased paired-pulse ratio and decreased spontaneous EPSC frequency, and is disrupted by α1 adrenergic receptor activation and by acute or chronic restraint stress. Electrophysiology in BNST slices, mGluR8 KO mice, selective agonists (DCPG), mGluR4 PAM (PHCCC), noradrenergic pharmacology, in vivo stress paradigm Neuropsychopharmacology High 21451497
2013 mGluR8 agonist DCPG decreases synaptic transmission but not LTP at thalamo-lateral amygdala synapses and selectively reduces contextual (but not cued) fear expression when injected intra-amygdala, while mGluR7 (not mGluR8) ablation attenuates thalamo-LA LTP and produces a general fear conditioning deficit. Electrophysiology in amygdala slices, mGluR7 and mGluR8 knockout mice, intra-amygdala pharmacology, fear-conditioned startle behavioral testing Neuropharmacology High 23664812
2016 mGluR8 functionally co-localizes with TRPA1 on cutaneous nociceptors; mGluR8 agonist DCPG reduces TRPA1-mediated Ca2+ mobilization and mechanical hypersensitivity, and this modulation occurs via the cAMP/PKA pathway. Ca2+ imaging with co-localization, behavioral paw withdrawal assay, single-fiber electrophysiology, PKA inhibitor (RpCAMPS) Neuroscience Medium 27497709
2018 Crystal structure of the human mGluR8 amino terminal domain (ATD) bound to L-AP4 or L-glutamate reveals that the phosphate group of L-AP4 contributes electronically and sterically to group III mGlu receptor selectivity; L-glutamate binds differently in mGlu1 vs. mGlu8 ATD. X-ray crystallography of recombinant human mGlu8 ATD Bioorganic & medicinal chemistry letters High 29402739
2018 Crystal structure of human mGluR8 ATD bound to (S)-DCPG reveals a uniquely large lobe opening angle, explaining the structural basis for DCPG's high mGlu8 subtype selectivity; this conformation differs substantially from homology models based on glutamate-bound mGlu1. X-ray crystallography of recombinant human mGlu8 ATD, comparative structural analysis and homology modeling Journal of medicinal chemistry High 30365309
2018 GRM8 transcriptional activation promotes squamous cell lung cancer (LUSC) cell survival through inhibition of cAMP pathway and activation of MAPK pathway; a GRM8 variant A112G activates downstream signaling and induces cell proliferation, reversed by cAMP stimulator and MEK inhibitor. CRISPR-Cas9 genome editing in patient-derived xenograft cells, whole exome/genome sequencing, pathway analysis, pharmacological rescue with cAMP stimulator and MEK inhibitor Cancer letters Medium 30391781
2018 mGluR8 downregulation in human neuroblastoma (SH-SY5Y) cells leads to faster proliferation and increased resistance to cytotoxic agents (staurosporine, doxorubicin, irinotecan, cisplatin) with lower caspase, calpain, GSK-3β, Akt, and JNK activities; mGluR8 overexpression in glioma cells decreases proliferation and increases apoptosis, establishing a tumor suppressor role. RNAi knockdown and cDNA overexpression in cancer cell lines, cell proliferation, migration, apoptosis, caspase/calpain/kinase activity assays Cancer letters Medium 29885518
2010 mGluR8 activation by DCPG reduces Off-light responses of retinal ganglion cells by suppressing both excitatory and inhibitory synaptic conductances, consistent with reduced glutamate release from bipolar cell terminals and possibly reduced inhibitory neurotransmitter release from amacrine cells; effect absent in mGluR8-deficient retinas. Extracellular and whole-cell light-evoked recording in wild-type and mGluR8-deficient mouse retinas Neuroscience Medium 20096339
2024 mGluR8 in parvalbumin-expressing thalamic reticular nucleus (TRN) neurons regulates excitatory drive onto dorsal thalamus relay cells and sensorimotor gating; constitutive PV-Cre mGluR8 knockout increases spontaneous excitatory input to dorsal thalamus and impairs prepulse inhibition, while AAV-mediated conditional TRN knockdown produces hyperlocomotion and anxiolytic behavior. Fluorescent in situ hybridization, conditional and cell-type-specific knockout (PV-Cre), AAV-mediated knockdown, ex vivo electrophysiology, behavioral testing (PPI, open field) The Journal of neuroscience High 38918065

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG. European journal of pharmacology 115 16324694
1998 Cloning and characterization of alternative mRNA forms for the rat metabotropic glutamate receptors mGluR7 and mGluR8. The European journal of neuroscience 108 9875342
2002 Closure of the Venus flytrap module of mGlu8 receptor and the activation process: Insights from mutations converting antagonists into agonists. Proceedings of the National Academy of Sciences of the United States of America 85 12151600
2002 Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor. Neuropharmacology 82 12213279
2005 Increased measures of anxiety and weight gain in mice lacking the group III metabotropic glutamate receptor mGluR8. The European journal of neuroscience 77 16045496
2002 Performance deficits of mGluR8 knockout mice in learning tasks: the effects of null mutation and the background genotype. Neuropharmacology 58 12213278
2009 Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 57 18618593
2005 Expression patterns of Group III metabotropic glutamate receptors mGluR4 and mGluR8 in multiple sclerosis lesions. Journal of neuroimmunology 56 15589052
2006 Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice. Neuropharmacology 53 17113112
1996 Presynaptic localization of a metabotropic glutamate receptor, mGluR8, in the rhinencephalic areas: a light and electron microscope study in the rat. Neuroscience letters 51 8710211
2007 Evaluation of the mGlu8 receptor as a putative therapeutic target in schizophrenia. Brain research 49 17434465
2008 The association analysis of RELN and GRM8 genes with autistic spectrum disorder in Chinese Han population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 48 17955477
2009 The effect of mGlu8 deficiency in animal models of psychiatric diseases. Genes, brain, and behavior 42 19740090
2004 Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 42 15211621
2002 Modulation of lateral perforant path excitatory responses by metabotropic glutamate 8 (mGlu8) receptors. Neuropharmacology 42 12213276
2018 Genomic sequencing and editing revealed the GRM8 signaling pathway as potential therapeutic targets of squamous cell lung cancer. Cancer letters 36 30391781
1996 Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. Genomics 35 8824806
2015 Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 34 26655190
2005 Differential roles of mGlu8 receptors in the regulation of glutamate and gamma-aminobutyric acid release at periaqueductal grey level. Neuropharmacology 34 16084932
2005 Effects of the mGluR8 agonist (S)-3,4-DCPG in the lateral amygdala on acquisition/expression of fear-potentiated startle, synaptic transmission, and plasticity. Neuropharmacology 33 16188284
2013 Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology. Neuropharmacology 32 23664812
2003 Systemic administration of the potent mGlu8 receptor agonist (S)-3,4-DCPG induces c-Fos in stress-related brain regions in wild-type, but not mGlu8 receptor knockout mice. Neuropharmacology 32 12907308
1997 The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1. Genomics 32 9299241
2018 Effects of Sub-Chronic MPTP Exposure on Behavioral and Cognitive Performance and the Microbiome of Wild-Type and mGlu8 Knockout Female and Male Mice. Frontiers in behavioral neuroscience 27 30072879
2003 Down-regulation of mGluR8 in pilocarpine epileptic rats. Synapse (New York, N.Y.) 26 12539201
2017 Decreased anxiety, voluntary ethanol intake and ethanol-induced CPP acquisition following activation of the metabotropic glutamate receptor 8 "mGluR8". Pharmacology, biochemistry, and behavior 25 28322866
2004 Potential antipsychotic and extrapyramidal effects of (R,S)-3,4-dicarboxyphenylglycine [(R,S)-3,4-DCPG], a mixed AMPA antagonist/mGluR8 agonist. Polish journal of pharmacology 24 15215559
2011 mGluR8 modulates excitatory transmission in the bed nucleus of the stria terminalis in a stress-dependent manner. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 23 21451497
2005 Lack of the antianxiety-like effect of (S)-3,4-DCPG, an mGlu8 receptor agonist, after central administration in rats. Pharmacological reports : PR 22 16382208
2002 Reduction of excitatory transmission in the retino-collicular pathway via selective activation of mGlu8 receptors by DCPG. Neuropharmacology 22 12213277
2018 An endogenous and ectopic expression of metabotropic glutamate receptor 8 (mGluR8) inhibits proliferation and increases chemosensitivity of human neuroblastoma and glioma cells. Cancer letters 19 29885518
2017 A 7q31.33q32.1 microdeletion including LRRC4 and GRM8 is associated with severe intellectual disability and characteristics of autism. Human genome variation 19 28224041
2008 Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the lateral olfactory tract-piriform cortex synapse. Neuropharmacology 19 18625254
2005 Interaction between mGluR8 and calcium channels in photoreceptors is sensitive to pertussis toxin and occurs via G protein betagamma subunit signaling. Investigative ophthalmology & visual science 18 15623786
2000 No association found between polymorphisms in genes encoding mGluR7 and mGluR8 and idiopathic generalised epilepsy in a case control study. Epilepsy research 16 10690750
2013 The role of rs2237781 within GRM8 in eating behavior. Brain and behavior 15 24392270
2012 Characterisation of an mGlu8 receptor-selective agonist and antagonist in the lateral and medial perforant path inputs to the dentate gyrus. Neuropharmacology 15 23220400
2013 Related functions of mGlu4 and mGlu8. Pharmacology, biochemistry, and behavior 14 23948069
2002 No association between metabotropic glutamate receptors 7 and 8 (mGlur7 and mGlur8) gene polymorphisms and withdrawal seizures and delirium tremens in alcohol-dependent individuals. Alcohol and alcoholism (Oxford, Oxfordshire) 14 11912074
2007 Anticonvulsive effect of a selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine (S-3,4-DCPG) in the mouse pilocarpine model of status epilepticus. Epilepsia 11 17430409
2018 Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4's group III mGlu receptor functional potency and selectivity. Bioorganic & medicinal chemistry letters 10 29402739
2015 Further Analyses of Genetic Association Between GRM8 and Alcohol Dependence Symptoms Among Young Adults. Journal of studies on alcohol and drugs 10 25978827
2024 Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism. Scientific reports 9 38849397
2014 Association analysis of the GRM8 gene with schizophrenia in the Uygur Chinese population. Hereditas 9 25588301
2018 Structural Basis for ( S)-3,4-Dicarboxyphenylglycine (DCPG) As a Potent and Subtype Selective Agonist of the mGlu8 Receptor. Journal of medicinal chemistry 8 30365309
2018 TCF4 and GRM8 gene polymorphisms and risk of schizophrenia in an Iranian population: a case-control study. Molecular biology reports 7 30288643
2021 The effect of the mGlu8 receptor agonist, (S)-3,4-DCPG on acquisition and expression of morphine-induced conditioned place preference in male rats. Behavioral and brain functions : BBF 6 33612106
2011 Depression of release by mGluR8 alters Ca2+ dependence of release machinery. Cerebral cortex (New York, N.Y. : 1991) 6 21903594
2010 Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses. Neuroscience 6 20096339
2018 Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic-Induced Human Neuroblastoma SH-SY5Y Cell Damage: The Impact of Cell Differentiation State. Basic & clinical pharmacology & toxicology 4 29753314
2016 Group III mGluR8 negatively modulates TRPA1. Neuroscience 4 27497709
2024 Rare CRHR2 and GRM8 variants identified as candidate factors associated with eating disorders in Japanese patients by whole exome sequencing. Heliyon 2 38644811
2016 Selective agonism of mGlu8 receptors by (S)-3,4-dicarboxyphenylglycine does not affect sleep stages in the rat. Pharmacological reports : PR 2 27914294
2025 Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus. Scientific reports 1 40133378
2025 Isoliquiritigenin as a Neuronal Radiation Mitigant: Mitigating Radiation-Induced Anhedonia Tendency Targeting Grik3/Grm8/Grin3a via Integrated Proteomics and AI-Driven Discovery. Pharmaceuticals (Basel, Switzerland) 1 41011178
2024 S-3,4-DCPG, a potent orthosteric agonist for the mGlu8 receptor, facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats. Pharmacology, biochemistry, and behavior 1 38653345
2009 Effects of (RS)-3,4-DCPG, a mixed AMPA antagonist/mGluR8 agonist, on aggressive behavior in mice. Revista de psiquiatria y salud mental 1 23034312
2025 Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β. Neuropharmacology 0 40010564
2024 Thalamocortical mGlu8 Modulates Dorsal Thalamus Excitatory Transmission and Sensorimotor Activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 38918065