Skip to main content
SpringerLink
Log in
Book cover

Encyclopedia of Signaling Molecules pp 24–35Cite as

5-Hydroxytryptamine Receptor 2C

  • Reference work entry
  • First Online:

  • 180 Accesses

Synonyms

5-HT1C; 5-HT2C; 5-Hydroxytryptamine (serotonin) receptor 2C, G protein coupled

Historical Background

The 5-hydroxytryptamine-type 2C receptor (5-HT2C, previously 5-HT1C) is one of the 14 G protein-coupled receptor subtypes activated by serotonin. 5-HT2C receptors are involved in a large variety of physiological functions such as nociception, motor behavior, endocrine secretion, thermoregulation, modulation of appetite, and the control of exchanges between the central nervous system and the cerebrospinal fluid. They have also been implicated in numerous pathologies such as schizophrenia, anxiety, depression, Parkinson’s disease, drug addiction, and obesity (Berg et al. 2008; Chagraoui et al. 2016). In line with their implication in various pathological situations, 5-HT2C receptors are considered as a major pharmacological target for the development of new treatments (see “Ligand-Dependent Nuclear Receptor Corepressor (LCoR)”) (Di Giovanni and De Deurwaerdere 2016).

With regard...

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abbas AI, Yadav PN, Yao WD, Arbuckle MI, Grant SG, Caron MG, Roth BL. PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptors. J Neurosci. 2009;29:7124–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Applegate CD, Tecott LH. Global increases in seizure susceptibility in mice lacking 5-HT2C receptors: a behavioral analysis. Exp Neurol. 1998;154:522–30.

    Article  PubMed  CAS  Google Scholar 

  • Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C. Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1. J Biol Chem. 2001;276:12974–82.

    Article  PubMed  CAS  Google Scholar 

  • Becamel C, Alonso G, Galeotti N, Demey E, Jouin P, Ullmer C, Dumuis A, Bockaert J, Marin P. Synaptic multiprotein complexes associated with 5-HT(2C) receptors: a proteomic approach. EMBO J. 2002;21:2332–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Becamel C, Gavarini S, Chanrion B, Alonso G, Galeotti N, Dumuis A, Bockaert J, Marin P. The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins. J Biol Chem. 2004;279:20257–66.

    Article  PubMed  CAS  Google Scholar 

  • Berg KA, Clarke WP, Cunningham KA, Spampinato U. Fine-tuning serotonin2c receptor function in the brain: molecular and functional implications. Neuropharmacology. 2008;55:969–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bigford GE, Chaudhry NS, Keane RW, Holohean AM. 5-Hydroxytryptamine 5HT2C receptors form a protein complex with N-methyl-D-aspartate GluN2A subunits and activate phosphorylation of Src protein to modulate motoneuronal depolarization. J Biol Chem. 2012;287:11049–59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P. Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res. 2006;326:553–72.

    Article  PubMed  CAS  Google Scholar 

  • Bonn M, Schmitt A, Lesch KP, Van Bockstaele EJ, Asan E. Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei. Brain Struct Funct. 2013;218:421–35.

    Article  PubMed  CAS  Google Scholar 

  • Brennan TJ, Seeley WW, Kilgard M, Schreiner CE, Tecott LH. Sound-induced seizures in serotonin 5-HT2c receptor mutant mice. Nat Genet. 1997;16:387–90.

    Article  PubMed  CAS  Google Scholar 

  • Bubar MJ, Cunningham KA. Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. Prog Brain Res. 2008;172:319–46.

    Article  PubMed  CAS  Google Scholar 

  • Bubar MJ, Stutz SJ, Cunningham KA. 5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway. PLoS One. 2011;6:e20508.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Buckland PR, Hoogendoorn B, Guy CA, Smith SK, Coleman SL, O’Donovan MC. Low gene expression conferred by association of an allele of the 5-HT2C receptor gene with antipsychotic-induced weight gain. Am J Psychiatry. 2005;162:613–5.

    Article  PubMed  Google Scholar 

  • Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC. The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen. Psychopharmacology. 2010;209:163–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Canal CE, Booth RG, Morgan D. Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse, selective 5-HT2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine elicited head-twitch response model. Neuropharmacology. 2013;70:112–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cassier E, Gallay N, Bourquard T, Claeysen S, Bockaert J, Crepieux P, Poupon A, Reiter E, Marin P, Vandermoere F. Phosphorylation of beta-arrestin2 at Thr383 by MEK underlies beta-arrestin-dependent activation of Erk1/2 by GPCRs. ELife. 2017;6:e23777.

    Google Scholar 

  • Chagraoui A, Thibaut F, Skiba M, Thuillez C, Bourin M. 5-HT2C receptors in psychiatric disorders: a review. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;66:120–35.

    Article  CAS  Google Scholar 

  • Chanrion B, Mannoury la Cour C, Gavarini S, Seimandi M, Vincent L, Pujol JF, Bockaert J, Marin P, Millan MJ. Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulation of cell surface expression and signal transduction. Mol Pharmacol. 2008;73:748–57.

    Article  CAS  PubMed  Google Scholar 

  • de Bodinat C, Guardiola-Lemaitre B, Mocaer E, Renard P, Munoz C, Millan MJ. Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov. 2010;9:628–42.

    Article  CAS  PubMed  Google Scholar 

  • De Deurwaerdere P, Navailles S, Berg KA, Clarke WP, Spampinato U. Constitutive activity of the serotonin2C receptor inhibits in vivo dopamine release in the rat striatum and nucleus accumbens. J Neurosci. 2004;24:3235–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deckert J, Meyer J, Catalano M, Bosi M, Sand P, DiBella D, Ortega G, Stober G, Franke P, Nothen MM, et al. Novel 5′-regulatory region polymorphisms of the 5-HT2C receptor gene: association study with panic disorder. Int J Neuropsychopharmacol. 2000;3:321–5.

    Article  CAS  PubMed  Google Scholar 

  • Del’Guidice T, Lemay F, Lemasson M, Levasseur-Moreau J, Manta S, Etievant A, Escoffier G, Dore FY, Roman FS, Beaulieu JM. Stimulation of 5-HT2C receptors improves cognitive deficits induced by human tryptophan hydroxylase 2 loss of function mutation. Neuropsychopharmacology. 2014;39:1125–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Di Giovanni G, De Deurwaerdere P. New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders. Pharmacol Ther. 2016;157:125–62.

    Article  CAS  PubMed  Google Scholar 

  • Fentress HM, Grinde E, Mazurkiewicz JE, Backstrom JR, Herrick-Davis K, Sanders-Bush E. Pharmacological properties of the Cys23Ser single nucleotide polymorphism in human 5-HT2C receptor isoforms. Pharmacogenomics J. 2005;5:244–54.

    Article  CAS  PubMed  Google Scholar 

  • Fossat P, Bacque-Cazenave J, De Deurwaerdere P, Cattaert D, Delbecque JP. Serotonin, but not dopamine, controls the stress response and anxiety-like behavior in the crayfish Procambarus clarkii. J Exp Biol. 2015;218:2745–52.

    Article  PubMed  Google Scholar 

  • Garfield AS, Davies JR, Burke LK, Furby HV, Wilkinson LS, Heisler LK, Isles AR. Increased alternate splicing of Htr2c in a mouse model for Prader-Willi syndrome leads disruption of 5HT2C receptor mediated appetite. Mol Brain. 2016;9:95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gavarini S, Becamel C, Altier C, Lory P, Poncet J, Wijnholds J, Bockaert J, Marin P. Opposite effects of PSD-95 and MPP3 PDZ proteins on serotonin 5-hydroxytryptamine2C receptor desensitization and membrane stability. Mol Biol Cell. 2006;17:4619–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Graves SM, Napier TC. SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats. BMC Neurosci. 2012;13:65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Heisler LK, Cowley MA, Kishi T, Tecott LH, Fan W, Low MJ, Smart JL, Rubinstein M, Tatro JB, Zigman JM, et al. Central serotonin and melanocortin pathways regulating energy homeostasis. Ann N Y Acad Sci. 2003;994:169–74.

    Article  CAS  PubMed  Google Scholar 

  • Heisler LK, Zhou L, Bajwa P, Hsu J, Tecott LH. Serotonin 5-HT(2C) receptors regulate anxiety-like behavior. Genes Brain Behav. 2007;6:491–6.

    Article  CAS  PubMed  Google Scholar 

  • Herrick-Davis K, Grinde E, Weaver BA. Serotonin 5-HT(2C) receptor homodimerization is not regulated by agonist or inverse agonist treatment. Eur J Pharmacol. 2007;568:45–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Herrick-Davis K, Grinde E, Lindsley T, Teitler M, Mancia F, Cowan A, Mazurkiewicz JE. Native serotonin 5-HT2C receptors are expressed as homodimers on the apical surface of choroid plexus epithelial cells. Mol Pharmacol. 2015;87:660–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Higgins GA, Fletcher PJ. Therapeutic potential of 5-HT2C receptor agonists for addictive disorders. ACS Chem Neurosci. 2015;6:1071–88.

    Article  CAS  PubMed  Google Scholar 

  • Howell LL, Cunningham KA. Serotonin 5-HT2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder. Pharmacol Rev. 2015;67:176–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jensen NH, Cremers TI, Sotty F. Therapeutic potential of 5-HT2C receptor ligands. ScientificWorldJournal. 2010;10:1870–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji SP, Zhang Y, Van Cleemput J, Jiang W, Liao M, Li L, Wan Q, Backstrom JR, Zhang X. Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse. Nat Med. 2006;12:324–9.

    Article  CAS  PubMed  Google Scholar 

  • Ji G, Zhang W, Mahimainathan L, Narasimhan M, Kiritoshi T, Fan X, Wang J, Green TA, Neugebauer V. 5-HT2C receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors. J Neurosci. 2017;37:1378–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Labasque M, Reiter E, Becamel C, Bockaert J, Marin P. Physical interaction of calmodulin with the 5-hydroxytryptamine2C receptor C-terminus is essential for G protein-independent, arrestin-dependent receptor signaling. Mol Biol Cell. 2008;19:4640–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Labasque M, Meffre J, Carrat G, Becamel C, Bockaert J, Marin P. Constitutive activity of Serotonin2C receptors at G protein-independent signaling: modulation by RNA editing and antidepressants. Mol Pharmacol. 2010;78:818–26.

    Article  CAS  PubMed  Google Scholar 

  • Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu DH, Virkkunen M, Weight F, Linnoila M, Goldman D. Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C). Genomics. 1995;27:274–9.

    Article  CAS  PubMed  Google Scholar 

  • Mancia F, Assur Z, Herman AG, Siegel R, Hendrickson WA. Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor. EMBO Rep. 2008;9:363–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marcinkiewcz CA, Mazzone CM, D’Agostino G, Halladay LR, Hardaway JA, DiBerto JF, Navarro M, Burnham N, Cristiano C, Dorrier CE, et al. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature. 2016;537:97–101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marion S, Weiner DM, Caron MG. RNA editing induces variation in desensitization and trafficking of 5-hydroxytryptamine 2c receptor isoforms. J Biol Chem. 2004;279:2945–54.

    Article  CAS  PubMed  Google Scholar 

  • McMahon LR, Filip M, Cunningham KA. Differential regulation of the mesoaccumbens circuit by serotonin 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Neurosci. 2001;21:7781–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer J, Saam W, Mossner R, Cangir O, Ortega GR, Tatschner T, Riederer P, Wienker TF, Lesch KP. Evolutionary conserved microsatellites in the promoter region of the 5-hydroxytryptamine receptor 2C gene (HTR2C) are not associated with bipolar disorder in females. J Neural Transm. 2002;109:939–46.

    Article  CAS  PubMed  Google Scholar 

  • Millan MJ. Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005;60:441–60.

    Article  PubMed  Google Scholar 

  • Miller KJ. Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity. Mol Interv. 2005;5:282–91.

    Article  CAS  PubMed  Google Scholar 

  • Morabito MV, Abbas AI, Hood JL, Kesterson RA, Jacobs MM, Kump DS, Hachey DL, Roth BL, Emeson RB. Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader-Willi syndrome. Neurobiol Dis. 2010;39:169–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moutkine I, Quentin E, Guiard BP, Maroteaux L, Doly S. Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT2C protomers. J Biol Chem. 2017;292:6352–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Neelakantan H, Holliday ED, Fox RG, Stutz SJ, Comer SD, Haney M, Anastasio NC, Moeller FG, Cunningham KA. Lorcaserin suppresses oxycodone self-administration and relapse vulnerability in rats. ACS chem Neurosci. 2017;6b00413.

    Google Scholar 

  • Nocjar C, Alex KD, Sonneborn A, Abbas AI, Roth BL, Pehek EA. Serotonin-2C and -2a receptor co-expression on cells in the rat medial prefrontal cortex. Neuroscience. 2015;297:22–37.

    Article  PubMed  CAS  Google Scholar 

  • Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med. 1998;4:1152–6.

    Article  CAS  PubMed  Google Scholar 

  • Nonogaki K, Abdallah L, Goulding EH, Bonasera SJ, Tecott LH. Hyperactivity and reduced energy cost of physical activity in serotonin 5-HT(2C) receptor mutant mice. Diabetes. 2003;52:315–20.

    Article  CAS  PubMed  Google Scholar 

  • Olaghere da Silva UB, Morabito MV, Canal CE, Airey DC, Emeson RB, Sanders-Bush E. Impact of RNA editing on functions of the serotonin 2C receptor in vivo. Front Neurosci. 2010;4:26.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Parker LL, Backstrom JR, Sanders-Bush E, Shieh BH. Agonist-induced phosphorylation of the serotonin 5-HT2C receptor regulates its interaction with multiple PDZ protein 1. J Biol Chem. 2003;278:21576–83.

    Article  CAS  PubMed  Google Scholar 

  • Risselada AJ, Vehof J, Bruggeman R, Wilffert B, Cohen D, Al Hadithy AF, Arends J, Mulder H. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study. Pharmacogenomics J. 2012;12:62–7.

    Article  CAS  PubMed  Google Scholar 

  • Sanders-Bush E, Fentress H, Hazelwood L. Serotonin 5-ht2 receptors: molecular and genomic diversity. Mol Interv. 2003;3:319–30.

    Article  CAS  PubMed  Google Scholar 

  • Song HR, Gu A, Schanen NC. Identification of a new polymorphism in the 3′-untranslated region of the human serotonin receptor 2C (5-HT2C) gene. Mol Genet Metab. 1999;66:224–7.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan LC, Clarke WP, Berg KA. Atypical antipsychotics and inverse agonism at 5-HT2 receptors. Curr Pharm Des. 2015;21:3732–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, Whelan K, Martin M, Morgan M, Chen W, et al. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther. 2008;325:577–87.

    Article  CAS  PubMed  Google Scholar 

  • Ullmer C, Schmuck K, Figge A, Lubbert H. Cloning and characterization of MUPP1, a novel PDZ domain protein. FEBS Lett. 1998;424:63–8.

    Article  CAS  PubMed  Google Scholar 

  • Werry TD, Loiacono R, Sexton PM, Christopoulos A. RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol Ther. 2008;119:7–23.

    Article  CAS  PubMed  Google Scholar 

  • Xiao H, Hapiak VM, Smith KA, Lin L, Hobson RJ, Plenefisch J, Komuniecki R. SER-1, a Caenorhabditis elegans 5-HT2-like receptor, and a multi-PDZ domain containing protein (MPZ-1) interact in vulval muscle to facilitate serotonin-stimulated egg-laying. Dev Biol. 2006;298:379–91.

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Berglund ED, Sohn JW, Holland WL, Chuang JC, Fukuda M, Rossi J, Williams KW, Jones JE, Zigman JM, et al. 5-HT(2C)Rs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci. 2010;13:1457–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yuan X, Yamada K, Ishiyama-Shigemoto S, Koyama W, Nonaka K. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes. Diabetologia. 2000;43:373–6.

    Article  CAS  PubMed  Google Scholar 

  • Zayara AE, McIver G, Valdivia PN, Lominac KD, McCreary AC, Szumlinski KK. Blockade of nucleus accumbens 5-HT2A and 5-HT2C receptors prevents the expression of cocaine-induced behavioral and neurochemical sensitization in rats. Psychopharmacology. 2011;213:321–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dépt. de Neurobiologie, Institut de Génomique Fonctionnelle, Université de Montpellier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, 141 rue de la Cardonille, F-34094, Montpellier Cedex 5, France

    Carine Bécamel, Philippe Marin & Joël Bockaert

Authors
  1. Carine Bécamel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philippe Marin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joël Bockaert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carine Bécamel .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Bécamel, C., Marin, P., Bockaert, J. (2018). 5-Hydroxytryptamine Receptor 2C. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_55

Download citation

Publish with us

Policies and ethics

Search

Navigation