Affinage

HTR2C

5-hydroxytryptamine receptor 2C · UniProt P28335

Length
458 aa
Mass
51.8 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HTR2C encodes a Gq-coupled serotonin receptor that functions as a central integrator of serotonergic signaling in the brain, governing feeding behavior, neuronal excitability, anxiety, cognitive flexibility, and dopaminergic tone. Upon serotonin binding, HTR2C activates phospholipase C to stimulate phosphoinositide hydrolysis and also engages a calcium/PLA2/lipoxygenase-dependent cGMP pathway; in hypothalamic POMC neurons it suppresses the M-current (KCNQ channels) to increase excitability, driving anorexia through downstream melanocortin-4 receptor signaling (PMID:7798914, PMID:22436698, PMID:18039773). The receptor forms constitutive homodimers beginning in the endoplasmic reticulum, undergoes extensive pre-mRNA editing regulated by snoRNA Snord115/MBII-52 that alters G protein coupling efficacy and constitutive activity, and is modulated by a physical interaction with PTEN that limits agonist-induced phosphorylation and thereby controls VTA dopaminergic output (PMID:16857671, PMID:19304781, PMID:16474401). Knockout mice exhibit obesity, spontaneous and audiogenic seizures, impaired dentate gyrus LTP, and loss of tonic inhibition of neuronal networks, while forebrain overexpression causes anxiety, collectively demonstrating that HTR2C calibrates excitability in GABAergic interneuron circuits across cortical, limbic, and subcortical regions (PMID:7700379, PMID:9241279, PMID:9844009, PMID:19614978).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Knockout studies established that HTR2C is required for normal feeding behavior control and tonic suppression of neuronal excitability, answering whether the receptor has non-redundant physiological roles in vivo.

    Evidence Targeted gene knockout in mice showing obesity and spontaneous seizures

    PMID:7700379

    Open questions at the time
    • Circuit identity of neurons mediating seizure susceptibility was not resolved
    • Whether obesity reflects central appetite regulation or peripheral metabolic effects was unclear
    • Downstream signaling pathways driving feeding phenotype uncharacterized
  2. 1995 High

    Identification of the cGMP signaling pathway downstream of HTR2C revealed that this receptor couples to effectors beyond canonical PLC/IP3, establishing multimodal second messenger engagement.

    Evidence Choroid plexus tissue slice assays with pharmacological inhibitors showing Ca²⁺/PLA2/lipoxygenase-dependent cGMP formation independent of Gi

    PMID:7798914

    Open questions at the time
    • Physiological relevance of cGMP signaling in neurons (vs. choroid plexus) not established
    • G protein identity for the cGMP arm not determined
  3. 1997 High

    Demonstration that constitutive activity arises from specific transmembrane mutations and that inverse agonists suppress basal signaling resolved how receptor conformation governs ligand-independent G protein coupling.

    Evidence Site-directed mutagenesis (S312F/K) with PI hydrolysis and radioligand binding in COS-7 cells

    PMID:9282936

    Open questions at the time
    • Whether naturally edited isoforms exhibit comparable constitutive activity was not tested
    • Structural basis for constitutive activation unknown
  4. 1997 High

    Audiogenic seizure susceptibility in knockout mice with subcortical c-fos mapping pinpointed HTR2C as a tonic brake on auditory circuit excitability, extending the seizure phenotype to a defined neural circuit.

    Evidence Knockout mouse audiogenic seizure testing with immediate early gene expression mapping

    PMID:9241279

    Open questions at the time
    • Cell-type-specific rescue not performed
    • Whether GABAergic interneuron loss of 5-HT2C is the causal mechanism remained untested
  5. 1998 High

    Selective impairment of dentate gyrus LTP in knockout mice established that HTR2C modulates synaptic plasticity at a specific hippocampal synapse, linking receptor function to spatial learning.

    Evidence Electrophysiology at four hippocampal pathways and Morris water maze in 5-HT2C null mice

    PMID:9844009

    Open questions at the time
    • Molecular mechanism of LTP modulation (pre- vs. postsynaptic) not determined
    • Whether effect is cell-autonomous in dentate neurons unknown
  6. 1999 Medium

    Discovery that RNA editing alters agonist-directed signaling (functional selectivity) at HTR2C established that post-transcriptional modification tunes receptor pharmacology in a ligand-dependent manner.

    Evidence Comparison of PI signaling by LSD and serotonin across edited and non-edited receptor isoforms

    PMID:10432492

    Open questions at the time
    • Which specific edited isoforms are present in vivo was not mapped
    • Structural basis for editing-induced signaling change unknown
    • Limited to PI readout; effects on other effectors not tested
  7. 2005 Medium

    Localization of HTR2C mRNA to GABAergic but not serotonergic neurons of the raphe nuclei provided the anatomical basis for a tonic inhibitory feedback loop controlling serotonin release.

    Evidence Double in situ hybridization for 5-HT2C and GAD mRNAs in rat raphe

    PMID:15652696

    Open questions at the time
    • Functional confirmation by cell-type-specific deletion not performed
    • Single-method anatomical study
  8. 2006 High

    FRET-based demonstration that HTR2C forms homodimers from the ER through the plasma membrane established dimerization as a constitutive biosynthetic feature rather than a ligand-induced event.

    Evidence Live-cell confocal FRET with CFP/YFP-tagged receptors and compartment-specific analysis

    PMID:16857671

    Open questions at the time
    • Functional consequence of preventing dimerization not tested
    • Whether heterodimers with other 5-HT2 subtypes form in vivo not addressed
  9. 2006 High

    Identification of PTEN as a physical interactor that dephosphorylates HTR2C and controls VTA dopaminergic output linked receptor phosphorylation status to drug reward behavior.

    Evidence Co-immunoprecipitation, Tat-3L4F interfering peptide, VTA electrophysiology, conditioned place preference

    PMID:16474401

    Open questions at the time
    • Whether PTEN acts via lipid or protein phosphatase activity at the receptor was not fully resolved
    • In vivo stoichiometry of the PTEN–5-HT2C complex unknown
  10. 2007 High

    Co-localization of HTR2C with POMC neurons and epistasis with MC4R knockout established that the anorexigenic effect of 5-HT2C agonism operates through the melanocortin pathway, resolving the downstream circuit for appetite suppression.

    Evidence Immunofluorescence co-localization in arcuate nucleus; MC4R KO mice unresponsive to 5-HT2C agonist hypophagia

    PMID:18039773

    Open questions at the time
    • Direct electrophysiological demonstration in POMC neurons came later
    • Contribution of non-POMC neuronal populations not excluded
  11. 2009 High

    Genetic ablation of snoRNA MBII-52 increased 5-HT2C RNA editing in vivo and altered impulsivity-related behaviors, establishing snoRNA-guided regulation as a physiologically relevant control mechanism for receptor function.

    Evidence PWS-IC mouse model with RNA editing quantification and behavioral pharmacology

    PMID:19304781

    Open questions at the time
    • Mechanism by which snoRNA inhibits editing enzyme access not resolved
    • Relative contribution of editing vs. splicing changes debated
  12. 2010 High

    Post-injury RNA editing shifts in spinal motoneurons produce constitutively active 5-HT2C isoforms that restore persistent calcium currents but cause spasticity, revealing a pathophysiological consequence of editing dysregulation.

    Evidence Spinal transection model with mRNA editing analysis, patch-clamp, and pharmacological blockade in rats and humans

    PMID:20512126

    Open questions at the time
    • Editing enzyme identity driving post-injury changes not identified
    • Long-term therapeutic safety of inverse agonist treatment not assessed
  13. 2012 High

    Electrophysiological recording in identified POMC neurons showed that HTR2C activation suppresses M-current (KCNQ), providing the ionic mechanism for 5-HT2C-mediated increase in POMC neuron excitability and feeding suppression.

    Evidence Visualized patch-clamp in POMC-EGFP transgenic mouse neurons with selective antagonist RS-102221

    PMID:22436698

    Open questions at the time
    • Signaling intermediates between Gq and KCNQ suppression not mapped
    • Whether M-current suppression also occurs in other HTR2C-expressing neurons not tested
  14. 2015 High

    Biophysical measurement confirmed native homodimeric stoichiometry and showed that maximal G protein activation requires dual-protomer agonist occupancy, establishing a functional consequence of dimerization.

    Evidence Fluorescence correlation spectroscopy with photon counting histogram analysis on native choroid plexus receptors and HEK293 cells

    PMID:25609374

    Open questions at the time
    • Whether dimerization interface residues are conserved across species not tested
    • Crystal or cryo-EM structure of the dimer not available
  15. 2022 High

    Patient-derived iPSC-GABAergic interneurons with reduced HTR2C expression showed increased firing and impaired calcium signaling, and genetic/pharmacological rescue reversed these deficits, causally linking diminished 5-HT2C signaling to interneuron dysfunction in major depression.

    Evidence iPSC differentiation to GABAergic interneurons from MDD patients, electrophysiology, calcium imaging, genetic rescue

    PMID:36373384

    Open questions at the time
    • Whether reduced HTR2C expression is a cause or consequence of disease epigenetic changes unclear
    • In vivo circuit-level validation in patients lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of the HTR2C homodimer, the precise signaling intermediates from Gq to KCNQ channel suppression, cell-type-specific contributions to seizure phenotypes, and the enzymatic mechanism by which editing enzymes are regulated by Snord115.
  • No cryo-EM or crystal structure of HTR2C dimer
  • Gq-to-KCNQ signaling cascade intermediates unmapped
  • Cell-type-specific conditional knockout studies across brain regions incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-112316 Neuronal System 7 R-HSA-162582 Signal Transduction 6
Partners
KCNQ2KCNQ3MC4RPTENSNORD115
Complex memberships
HTR2C homodimer

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 5-HT2C receptor knockout mice develop obesity due to abnormal control of feeding behavior and are prone to spontaneous seizures, establishing roles for this receptor in serotonergic control of appetite and tonic inhibition of neuronal network excitability. Targeted gene knockout in mice with behavioral and physiological phenotypic readouts Nature High 7700379
1997 5-HT2C receptor null mutant mice are extremely susceptible to audiogenic seizures with complete penetrance in adults, and immediate early gene expression indicates seizures are subcortical phenomena in auditory circuits, implicating 5-HT2C receptors in serotoninergic control of epilepsy. Knockout mouse model, audiogenic seizure testing, immediate early gene expression (c-fos) Nature genetics High 9241279
1997 Site-directed mutagenesis of serine 312 to phenylalanine or lysine in the 5-HT2C receptor produces constitutively active receptors that spontaneously couple to G proteins and stimulate phosphatidylinositol (PI) hydrolysis in the absence of agonist; inverse agonists mianserin and mesulergine decrease basal PI hydrolysis of the S312K mutant. Site-directed mutagenesis, radioligand binding, PI hydrolysis assay in COS-7 cells Journal of neurochemistry High 9282936
1995 5-HT2C receptor activation in choroid plexus stimulates cyclic GMP (cGMP) formation in addition to phosphoinositide turnover; cGMP formation is calcium-, phospholipase A2-, and lipoxygenase-dependent and not inhibited by pertussis toxin, indicating coupling through a Gi-independent pathway. Choroid plexus tissue slice assay, cGMP measurement, pharmacological antagonism, pertussis toxin pretreatment, enzyme inhibitors Journal of neurochemistry High 7798914
1995 The rat 5-HT2C receptor is a glycoprotein containing N-linked oligosaccharides; N-linked sugars contribute approximately 30% of the relative mass, and sialic acid residues associate with 5-HT2C receptors in the choroid plexus but not in a recombinant cell line. Western blotting with anti-5-HT2C antibodies, tunicamycin metabolic inhibition, N-glycosidase F and neuraminidase enzymatic treatments Brain research. Molecular brain research High 8750891
1998 5-HT2C receptor mutant mice show selective impairment of long-term potentiation at medial perforant path-dentate gyrus synapses and exhibit abnormal Morris water maze performance and reduced aversion to novel environments, establishing a role for 5-HT2C receptors in dentate gyrus synaptic plasticity. Knockout mouse model, LTP electrophysiology at four hippocampal regions, Morris water maze, behavioral assays Proceedings of the National Academy of Sciences of the United States of America High 9844009
1999 Inverse agonists at 5-HT2C receptors expressed at physiological density do not reduce basal inositol phosphate (IP) accumulation but selectively enhance 5-HT2C-mediated IP accumulation (not arachidonic acid release) after prolonged treatment; this enhancement may involve increased expression of Gαq/11 and possibly Gα12 and Gα13 proteins. IP accumulation assay, arachidonic acid release assay, pharmacological characterization in CHO cells, G protein expression analysis Molecular pharmacology Medium 10220565
1999 Agonist-directed signaling (functional selectivity) at 5-HT2C receptors: LSD and serotonin differ in their activation of phosphatidylinositol signaling; RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate PI signaling. Phosphatidylinositol signaling assay, comparison of edited vs. non-edited receptor isoforms Neuropsychopharmacology Medium 10432492
2006 PTEN physically interacts with the third intracellular loop (3L4F region) of the 5-HT2C receptor and limits agonist-induced phosphorylation of the receptor through its protein phosphatase activity; disruption of this PTEN:5-HT2cR complex by a Tat-3L4F interfering peptide suppresses VTA dopaminergic neuron firing and blocks conditioned place preference for THC and nicotine. Co-immunoprecipitation in cell cultures, interfering peptide (Tat-3L4F), electrophysiology of VTA neurons, conditioned place preference behavioral tests Nature medicine High 16474401
2006 5-HT2C receptor homodimerization/oligomerization begins in the endoplasmic reticulum and persists through Golgi and plasma membrane, as demonstrated by real-time FRET between CFP- and YFP-tagged receptors in intact living cells, suggesting dimer formation is a step in receptor maturation. Confocal fluorescence resonance energy transfer (FRET), acceptor photobleaching, live-cell time-lapse confocal imaging The Journal of biological chemistry High 16857671
2007 5-HT2C receptors are co-localized with GABA neurons (GAD-positive) and dopamine neurons (tyrosine hydroxylase-positive) in the VTA, establishing the anatomical basis for 5-HT2C-mediated inhibitory control of both GABAergic and dopaminergic output in the mesolimbic system. Double-label immunofluorescence in rat VTA tissue Neuroscience Medium 17367945
2007 5-HT2C receptors are coexpressed with proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus; melanocortin 4 receptor (MC4R) knockout mice are unresponsive to 5-HT2CR agonist-induced hypophagia, establishing MC4R as a requisite downstream pathway for 5-HT2CR agonist control of food intake. Immunofluorescence co-localization, MC4R knockout mice, pharmacological feeding studies Endocrinology High 18039773
2010 After spinal cord injury, post-transcriptional RNA editing of 5-HT2C receptor mRNA increases constitutively active receptor isoforms in motoneurons; this constitutive activity restores persistent calcium currents and enables locomotor recovery but also underlies muscle spasms; blocking constitutively active 5-HT2C receptors with SB206553 or cyproheptadine eliminates these currents and spasms. In vivo spinal transection model, mRNA editing analysis, patch-clamp electrophysiology in rats, pharmacological blockade in rats and humans Nature medicine High 20512126
2009 Loss of the imprinted snoRNA mbii-52 leads to increased editing (but not alternative splicing) of 5-HT2C receptor pre-mRNA in mice, resulting in altered 5-HT2CR-related behaviors including impulsive responding, locomotor activity, and palatable food reactivity, confirming mbii-52 as a negative regulator of 5-HT2C receptor RNA editing in vivo. PWS-IC+/- mouse model (mbii-52 knockout), RNA editing analysis, behavioral testing with pharmacological validation Human molecular genetics High 19304781
2012 5-HT2C receptor activation suppresses the M-current (KCNQ channel-mediated) in hypothalamic POMC neurons via a mechanism requiring 5-HT2C receptors (blocked by RS-102221), thereby increasing POMC neuronal excitability to reduce food intake. Visualized patch-clamp recording in POMC-EGFP transgenic mice neurons, pharmacological agonists and selective antagonist RS-102221 American journal of physiology. Endocrinology and metabolism High 22436698
2015 Native 5-HT2C receptors in choroid plexus epithelial cells exist as homodimers on the apical surface; fluorescence correlation spectroscopy with photon counting histogram molecular brightness analysis demonstrated homodimeric structure; agonist binding to one protomer activates G protein signaling, but maximal stimulation requires occupancy of both protomers. Fluorescence correlation spectroscopy (FCS) with photon counting histogram (PCH), anti-5-HT2C Fab protein, molecular brightness analysis, wash-resistant agonist occupancy experiments in HEK293 cells Molecular pharmacology High 25609374
2003 PNU-69176E is a positive allosteric modulator of the human 5-HT2C receptor that enhances [3H]5-HT binding by increasing agonist affinity and renders receptors constitutively active (as measured by GTPγS binding, IP3 release, and IP accumulation) without affecting antagonist binding; this action is selective for 5-HT2C over related receptors (5-HT2A, 5-HT2B, 5-HT6, 5-HT7, D2, D3). Radioligand binding, GTPγS binding, IP3 assay, inositol phosphate accumulation in multiple cell lines expressing human 5-HT2C Molecular pharmacology High 12815163
1996 5-HT2C receptor stimulation in the subthalamic nucleus is sufficient to elicit orofacial dyskinesia; bilateral subthalamic infusion of selective 5-HT2C antagonists blocks systemically-induced oral movements, establishing the subthalamic nucleus as a key anatomical site for 5-HT2C-mediated oral dyskinesia. Local stereotaxic infusion into subthalamic nucleus, systemic drug administration, pharmacological antagonism in rats Neuroscience High 8730711
2010 5-HT2C receptor antagonism in the orbitofrontal cortex (OFC), but not the medial prefrontal cortex or nucleus accumbens, improves spatial reversal learning by reducing perseverative errors, establishing the OFC as the neuroanatomical locus for 5-HT2C-mediated cognitive flexibility. Targeted intracerebral microinfusions into OFC, mPFC, and NAc in rats; spatial reversal learning task The Journal of neuroscience High 20089901
2010 5-HT2C receptors on alveolar macrophages mediate serotonin-induced calcium influx and CCL2 (MCP-1) production; these responses are absent in alveolar macrophages from 5-HT2C-deficient mice, demonstrating a functional role for 5-HT2C in macrophage immune activation. qPCR, calcium imaging, ELISA/dot-blot for CCL2, microarray, 5-HT2C knockout mouse alveolar macrophages, selective inhibitor RS-102221 American journal of physiology. Lung cellular and molecular physiology High 20495077
2009 Overexpression of 5-HT2C receptors in forebrain (cortex and limbic regions) under CaMKIIα promoter in transgenic mice causes elevated anxiety-like behavior and hypoactivity without exogenous ligand stimulation, demonstrating that increased 5-HT2C receptor signaling is causative for anxiety phenotypes. Transgenic mouse overexpression, elevated plus-maze, wheel-running, novel environment activity testing The European journal of neuroscience High 19614978
2019 5-HT2C receptor signaling in the lateral habenula (LHb) contributes to alcohol withdrawal-induced anxiety; LHb 5-HT2CR protein and serotonin turnover are elevated in post-ethanol rats; intra-LHb 5-HT2CR antagonism alleviates anxiety-like behaviors and increases KCNQ2/3 membrane protein expression, indicating 5-HT2CR interacts with M-channels to regulate LHb excitability. Intra-LHb microinfusion of selective agonist/antagonist, elevated plus-maze, open-field, marble burying, c-Fos immunostaining, Western blotting for KCNQ2/3, operant alcohol self-administration Neuropharmacology High 31778691
2005 5-HT2C receptor mRNA is expressed in GABAergic neurons (glutamic acid decarboxylase-positive) but not in serotonergic neurons of the dorsal and median raphe nuclei, providing anatomical support for a negative feedback loop in which 5-HT2C-expressing GABAergic interneurons suppress 5-HT cell firing. Double in situ hybridization in rat brain sections Journal of chemical neuroanatomy Medium 15652696
2022 iPSC-derived GABAergic interneurons from MDD patients with suicidal behavior show decreased 5-HT2C receptor expression, increased neural firing, and weakened calcium signaling; pharmacological activation or genetic restoration of 5-HT2C receptor rescues neuronal activity deficits, establishing a causal role for reduced 5-HT2C signaling in abnormal interneuron activity in depression. iPSC differentiation to GABAergic interneurons and ventral forebrain organoids, electrophysiology, calcium imaging, transcriptomic sequencing, 5-HT2C agonist and genetic rescue EMBO molecular medicine High 36373384
1996 Fluoxetine, norfluoxetine, and citalopram act as antagonists (not inverse agonists) at the 5-HT2C receptor in radioligand binding and phosphoinositide hydrolysis assays, with 10- to 23-fold selectivity for 5-HT2C over 5-HT2A receptors in vitro. Radioligand binding assays, phosphoinositide hydrolysis assay in clonal cell line and rat choroid plexus Psychopharmacology High 8876023
2016 Loss of Snord115 (the mouse mbii-52 ortholog) increases levels of truncated/alternatively spliced hypothalamic 5-HT2C receptor pre-mRNA, reduces POMC mRNA in the arcuate nucleus, and renders mice unresponsive to 5-HT2C agonist-induced anorexia with attenuated activation of POMC neurons, demonstrating that Snord115-regulated 5-HT2C mRNA processing is required for normal 5-HT2C-POMC appetite control. PWS-IC mouse model, RT-PCR for splicing isoforms, in situ hybridization for POMC mRNA, c-Fos immunostaining of POMC neurons, pharmacological feeding studies Molecular brain High 27931246
2006 WAY-161503 is a functional agonist at 5-HT2C receptors stimulating both phospholipase C (IP formation, calcium mobilization) and phospholipase A2 (arachidonic acid release) pathways, with higher potency and efficacy for PLC than PLA2, demonstrating biased signaling at the 5-HT2C receptor. Radioligand binding, inositol phosphate accumulation assay, calcium mobilization assay, arachidonic acid release assay in CHO cells Brain research High 16430874

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 1038 7700379
2010 Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors. Nature medicine 327 20512126
2005 Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie 214 16433010
2007 Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology 199 18039773
2007 Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. The international journal of neuropsychopharmacology 175 17477888
2003 5-HT2A and 5-HT2C receptors and their atypical regulation properties. Life sciences 175 12650852
1996 Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology 172 8876023
2001 Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology 159 11489456
1994 In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. British journal of pharmacology 157 7912626
2007 Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience 139 17367945
2009 Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour. Human molecular genetics 133 19304781
2003 Serotonin and drug reward: focus on 5-HT2C receptors. European journal of pharmacology 132 14623358
1997 Sound-induced seizures in serotonin 5-HT2c receptor mutant mice. Nature genetics 132 9241279
1996 Increased 5-HT2C receptor responsiveness occurs on rearing rats in social isolation. Psychopharmacology 119 8867874
2006 Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse. Nature medicine 117 16474401
1999 Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist. British journal of pharmacology 115 10188965
2006 The 5-HT2C receptor and antipsychoticinduced weight gain - mechanisms and genetics. Journal of psychopharmacology (Oxford, England) 114 16785265
2010 Enhancement of spatial reversal learning by 5-HT2C receptor antagonism is neuroanatomically specific. The Journal of neuroscience : the official journal of the Society for Neuroscience 111 20089901
2002 Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety. Pharmacology, biochemistry, and behavior 111 11888553
2005 The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Progress in neuro-psychopharmacology & biological psychiatry 105 15953671
2011 Mode of action of agomelatine: synergy between melatonergic and 5-HT2C receptors. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 103 21999473
2007 Association of the HTR2C gene and antipsychotic induced weight gain: a meta-analysis. The international journal of neuropsychopharmacology 97 17291373
2006 Serotonin 5-HT2C receptor homodimer biogenesis in the endoplasmic reticulum: real-time visualization with confocal fluorescence resonance energy transfer. The Journal of biological chemistry 94 16857671
2003 Compulsive behavior in the 5-HT2C receptor knockout mouse. Physiology & behavior 94 12782219
2005 Expression of serotonin 5-HT2C receptors in GABAergic cells of the anterior raphe nuclei. Journal of chemical neuroanatomy 89 15652696
2010 Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics 88 21121776
1998 Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice. Annals of the New York Academy of Sciences 87 9928241
2015 5-HT2C receptors in psychiatric disorders: A review. Progress in neuro-psychopharmacology & biological psychiatry 85 26739950
2015 New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders. Pharmacology & therapeutics 84 26617215
1998 Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice. Proceedings of the National Academy of Sciences of the United States of America 83 9844009
1999 Novel actions of inverse agonists on 5-HT2C receptor systems. Molecular pharmacology 82 10220565
2001 Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement. Psychopharmacology 81 11205420
1998 Serotonin 5-HT2c agonists mimic the effect of light pulses on circadian rhythms. Brain research 81 9739147
2007 Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents. Psychopharmacology 78 17297636
2009 Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors. Psychopharmacology 75 19688201
2007 Stimulation of 5-HT2C receptors attenuates cue and cocaine-primed reinstatement of cocaine-seeking behavior in rats. Behavioural pharmacology 75 17989517
2007 The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. Journal of clinical psychopharmacology 73 17632216
2015 Therapeutic Potential of 5-HT2C Receptor Agonists for Addictive Disorders. ACS chemical neuroscience 72 25870913
1999 Effects of the 5-HT2C/2B antagonist SB 206553 on hyperactivity induced by cocaine. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 72 10327425
1996 A role for the subthalamic nucleus in 5-HT2C-induced oral dyskinesia. Neuroscience 72 8730711
2013 From obesity to substance abuse: therapeutic opportunities for 5-HT2C receptor agonists. Trends in pharmacological sciences 71 24041919
2005 Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity. Molecular interventions 71 16249524
2009 HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: a replication study. Journal of clinical psychopharmacology 70 19142101
2010 Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 67 20504252
1999 Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests. American journal of medical genetics 67 10206238
1994 Evidence that 5-HT2c receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety. Psychopharmacology 66 7846211
2010 Therapeutic potential of 5-HT2C receptor ligands. TheScientificWorldJournal 60 20852829
1995 Further evidence that fluoxetine interacts with a 5-HT2C receptor in glial cells. Brain research bulletin 60 7583341
2006 Antiobesity-like effects of the 5-HT2C receptor agonist WAY-161503. Brain research 57 16430874
2005 Serotonergic 5-HT2C receptors as a potential therapeutic target for the design antiepileptic drugs. Current topics in medicinal chemistry 57 15638778
2015 Role of serotonin 5-HT2C and histamine H1 receptors in antipsychotic-induced diabetes: A pharmacoepidemiological-pharmacodynamic study in VigiBase. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 54 26256010
1995 Serotonin 5-HT2C receptor stimulates cyclic GMP formation in choroid plexus. Journal of neurochemistry 53 7798914
2014 Critical involvement of 5-HT2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats. Psychopharmacology 52 25417553
2010 Serotonin activates murine alveolar macrophages through 5-HT2C receptors. American journal of physiology. Lung cellular and molecular physiology 51 20495077
1997 Activating mutations of the serotonin 5-HT2C receptor. Journal of neurochemistry 51 9282936
1996 Moderate dieting causes 5-HT2C receptor supersensitivity. Psychological medicine 51 8931161
2006 The potential use of selective 5-HT2C agonists in treating obesity. Expert opinion on investigational drugs 49 16503763
2022 Depressive patient-derived GABA interneurons reveal abnormal neural activity associated with HTR2C. EMBO molecular medicine 48 36373384
2010 Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study. The pharmacogenomics journal 47 20680028
2004 The 5-HT2C receptor as a target for mood disorders. Expert opinion on therapeutic targets 47 14996615
2006 Serotonin involvement in the basal ganglia pathophysiology: could the 5-HT2C receptor be a new target for therapeutic strategies? Current medicinal chemistry 46 17073648
1999 HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses. Biological psychiatry 46 10494451
2009 Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene. The pharmacogenomics journal 45 19434072
2011 Control of hippocampal theta rhythm by serotonin: role of 5-HT2c receptors. Neuropharmacology 44 21281651
2004 Chronic treatment with fluvoxamine desensitizes 5-HT2C receptor-mediated hypolocomotion in rats. Pharmacology, biochemistry, and behavior 44 15301922
1999 Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD). Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 44 10432492
2015 The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study. Psychopharmacology 42 26007324
2006 The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study. The pharmacogenomics journal 42 17016522
1996 Chronic citalopram and fluoxetine treatments upregulate 5-HT2c receptors in the rat choroid plexus. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 42 8840350
2019 Anxiety during alcohol withdrawal involves 5-HT2C receptors and M-channels in the lateral habenula. Neuropharmacology 41 31778691
2015 Native serotonin 5-HT2C receptors are expressed as homodimers on the apical surface of choroid plexus epithelial cells. Molecular pharmacology 41 25609374
2007 Activation of the serotonin 5-HT2C receptor is involved in the enhanced anxiety in rats after single-prolonged stress. Pharmacology, biochemistry, and behavior 41 18067955
1998 Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action. Psychopharmacology 40 9683007
2016 Increased alternate splicing of Htr2c in a mouse model for Prader-Willi syndrome leads disruption of 5HT2C receptor mediated appetite. Molecular brain 38 27931246
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