Skip to main content
SpringerLink
Log in

5-HT2B Receptors and Antidepressants

  • Chapter
  • First Online:
5-HT2B Receptors

Part of the book series: The Receptors ((REC,volume 35))

  • 384 Accesses

Abstract

Among several serotonin receptors, the 5-HT2B is one of the less studied in the brain. Although this receptor is only weakly expressed in the nervous system, it appears to be involved in several biological mechanisms linked to neuropsychiatric dysfunctions and/or action of several drugs. Indeed, the selective serotonin reuptake inhibitors (SSRIs) act by blocking the serotonin transporter, but their acute and chronic effects are specifically blunted when the 5-HT2B receptor is pharmacologically blocked or when its gene is knocked-out. This lack of effect is also observed in mice submitted to chronic stress paradigms that induce depressive-like states. On the contrary, response to non-serotonergic antidepressants are conserved in mice lacking a functional 5-HT2B receptor. Recent studies have demonstrated that 5-HT2B receptors are expressed by serotonergic neurons, and that they can act as positive autoreceptors, counterbalancing the actions of the negative 5-HT1A autoreceptors. In addition, elegant studies confirm that it is the 5-HT2B autoreceptor that is required for SSRIs effects. All in all, the specific lack of responses to SSRIs exhibited by mice knocked-out for the 5-HT2B receptor make these animals an ideal model for the study of resistance to SSRIs antidepressants, a condition highly reported in clinics. Besides, the impaired response to serotonergic antidepressants, mice constitutively lacking the 5-HT2B receptor have increased basal levels of BDNF in the hippocampus. The “antidepressant-like phenotype” exhibited by these mice offers an interesting tool for the study of new molecules potentially acting as antidepressants.

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

Access this chapter

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

Institutional subscriptions

Abbreviations

5-Hydroxytryptamine, 5-HT:

Serotonin

DRN:

Dorsal raphe nucleus

FST:

Forced swimming test

GIRK:

G protein-coupled inwardly-rectifying potassium channels

KO:

Knock-out

NSF:

novelty suppressed feeding

SERT:

Serotonin transporter

SNP:

Single-nucleotide polymorphism

SSRIs:

Selective serotonin reuptake inhibitors

TPH2:

Tryptophan hydroxylase

UCMS:

Unpredictable chronic mild stress

VMAT2:

Vesicular monoamine transporter

References

  1. Okaty BW, Freret ME, Rood BD, Brust RD, Hennessy ML, Debairos D et al (2015) Multi-scale molecular deconstruction of the serotonin neuron system. Neuron 88(4):774–791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Commons KG (2016) Ascending serotonin neuron diversity under two umbrellas. Brain Struct Funct 221(7):3347–3360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Riad M, Garcia S, Watkins KC, Jodoin N, Doucet E, Langlois X et al (2000) Somatodendritic localization of 5-HT1A and preterminal axonal localization of 5-HT1B serotonin receptors in adult rat brain. J Comp Neurol 417(2):181–194

    Article  CAS  PubMed  Google Scholar 

  4. Aghajanian GK, Lakoski JM (1984) Hyperpolarization of serotonergic neurons by serotonin and LSD: studies in brain slices showing increased K+ conductance. Brain Res 305(1):181–185

    Article  CAS  PubMed  Google Scholar 

  5. Andrade R, Huereca D, Lyons JG, Andrade EM, Mcgregor KM (2015) 5-HT1A receptor-mediated autoinhibition and the control of serotonergic cell firing. ACS Chem Neurosci 6(7):1110–1115

    Article  CAS  PubMed  Google Scholar 

  6. Craven RM, Grahame-Smith DG, Newberry NR (2001) 5-HT1A and 5-HT2 receptors differentially regulate the excitability of 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro. Brain Res 899(1-2):159–168

    Article  CAS  PubMed  Google Scholar 

  7. Kirby LG, Pernar L, Valentino RJ, Beck SG (2003) Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies. Neuroscience 116(3):669–683

    Article  CAS  PubMed  Google Scholar 

  8. Liu R, Jolas T, Aghajanian G (2000) Serotonin 5-HT2 receptors activate local GABA inhibitory inputs to serotonergic neurons of the dorsal raphe nucleus. Brain Res 873(1):34–45

    Article  CAS  PubMed  Google Scholar 

  9. Boothman LJ, Allers KA, Rasmussen K, Sharp T (2003) Evidence that central 5-HT2A and 5-HT(2B/C) receptors regulate 5-HT cell firing in the dorsal raphe nucleus of the anaesthetised rat. Br J Pharmacol 139(5):998–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Quérée P, Peters S, Sharp T (2009) Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. Br J Pharmacol 158(6):1477–1485

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Leon-Pinzon C, Cercós MG, Noguez P, Trueta C, De-Miguel FF (2014) Exocytosis of serotonin from the neuronal soma is sustained by a serotonin and calcium-dependent feedback loop. Front Cell Neurosci 8:169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Marinelli S, Schnell SA, Hack SP, Christie MJ, Wessendorf MW, Vaughan CW (2004) Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and electrophysiologically heterogeneous. J Neurophysiol 92(6):3532–3537

    Article  CAS  PubMed  Google Scholar 

  13. Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T et al (2010) A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature 468(8):1061–1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Doly S, Bertran-Gonzalez J, Callebert J, Bruneau A, Banas SM, Belmer A et al (2009) Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice. PLoS ONE 4(11):e7952

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Doly S, Valjent E, Setola V, Callebert J, Herve D, Launay JM et al (2008) Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro. J Neurosci 28(11):2933–2940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Banas SM, Doly S, Boutourlinsky K, Diaz SL, Belmer A, Callebert J et al (2011) Deconstructing antiobesity compound action: requirement of serotonin 5-HT2B receptors for dexfenfluramine anorectic effects. Neuropsychopharmacology 36(2):423–433

    Article  CAS  PubMed  Google Scholar 

  17. Loric S, Launay J-M, Colas J-F, Maroteaux L (1992) New mouse 5-HT2-like receptor: expression in brain, heart, and intestine. FEBS L 312:203–207

    Article  CAS  Google Scholar 

  18. Kursar JD, Nelson DL, Wainscott D, Baez M (1994) Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor. Mol Pharmacol 46:227–234

    CAS  PubMed  Google Scholar 

  19. Choi D-S, Birraux G, Launay J-M, Maroteaux L (1994) The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors. FEBS L 352:393–399

    Article  CAS  Google Scholar 

  20. Bonhaus DW, Bach C, DeSouza A, Salazar FHR, Matsuoka BD, Zuppan P et al (1995) The pharmacology and distribution of human 5-hydroxytryptamine 2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol 115:622–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bonaventure P, Guo H, Tian B, Liu X, Bittner A, Roland B et al (2002) Nuclei and subnuclei gene expression profiling in mammalian brain. Brain Res 943(1):38–47

    Article  CAS  PubMed  Google Scholar 

  22. Diaz SL, Doly S, Narboux-Nême N, Fernandez S, Mazot P, Banas S et al (2012) 5-HT2B receptors are required for serotonin-selective antidepressant actions. Mol Psychiatry 17:154–163

    Article  CAS  PubMed  Google Scholar 

  23. Kalueff AV, LaPorte JL, Murphy DL (2008) Perspectives on genetic animal models of serotonin toxicity. Neurochem Int 52(4-5):649–658

    Article  CAS  PubMed  Google Scholar 

  24. Van Oekelen D, Megens A, Meert T, Luyten WH, Leysen JE (2002) Role of 5-HT2 receptors in the tryptamine-induced 5-HT syndrome in rats. Behav Pharmacol 13(4):313–318

    Article  PubMed  Google Scholar 

  25. Scotton WJ, Hill LJ, Williams AC, Barnes NM (2019) Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions. Int J Tryptophan Res 12:1178646919873925

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kennett GA, Dickinson SL, Curzon G (1985) Central serotonergic responses and behavioural adaptation to repeated immobilisation: the effect of the corticosterone synthesis inhibitor metyrapone. Eur J Pharmacol 119(3):143–152

    Article  CAS  PubMed  Google Scholar 

  27. Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T (2006) Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. Eur J Pharmacol 532(3):258–264

    Article  CAS  PubMed  Google Scholar 

  28. Sternbach H (1991) The serotonin syndrome. Am J Psychiatry 148(6):705–713

    Article  CAS  PubMed  Google Scholar 

  29. Fox MA, Jensen CL, Gallagher PS, Murphy DL (2007) Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology 53(5):643–656

    Article  CAS  PubMed  Google Scholar 

  30. Haberzettl R, Bert B, Fink H, Fox MA (2013) Animal models of the serotonin syndrome: a systematic review. Behav Brain Res 256:328–345

    Article  CAS  PubMed  Google Scholar 

  31. Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7(2):137–151

    Article  CAS  PubMed  Google Scholar 

  32. Wong ML, Licinio J (2004) From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat Rev Drug Discov 3(2):136–151

    Article  CAS  PubMed  Google Scholar 

  33. Schafer WR (1999) How do antidepressants work? prospects for genetic analysis of drug mechanisms. Cell 98(5):551–554

    Article  CAS  PubMed  Google Scholar 

  34. Miller KJ, Hoffman BJ (1994) Adenosine A3 receptors regulate serotonin transport via nitric oxide and cGMP. J Biol Chem 269(44):27351–27356

    Article  CAS  PubMed  Google Scholar 

  35. Prasad HC, Zhu CB, McCauley JL, Samuvel DJ, Ramamoorthy S, Shelton RC et al (2005) Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. Proc Natl Acad Sci USA 102(32):11545–11550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lucki I, Dalvi A, Mayorga AJ (2001) Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology 155(3):315–322

    Article  CAS  PubMed  Google Scholar 

  37. Da-Rocha MA Jr, Puech AJ, Thiebot MH (1997) Influence of anxiolytic drugs on the effects of specific serotonin reuptake inhibitors in the forced swimming test in mice. J Psychopharm 11(3):211–218

    Article  CAS  Google Scholar 

  38. David DJP, Renard CE, Jolliet P, Hascoët M, Bourin M (2003) Antidepressant-like effects in various mice strains in the forced swimming test. Psychopharmacology 166(4):373–382

    Article  CAS  PubMed  Google Scholar 

  39. Bortolozzi A, Amargós-Bosch M, Toth M, Artigas F, Adell A (2004) In vivo efflux of serotonin in the dorsal raphe nucleus of 5-HT1A receptor knockout mice. J Neurochem 88(6):1373–1379

    Article  CAS  PubMed  Google Scholar 

  40. Jones MD, Lucki I (2005) Sex differences in the regulation of serotonergic transmission and behavior in 5-HT receptor knockout mice. Neuropsychopharmacology 30(6):1039–1047

    Article  CAS  PubMed  Google Scholar 

  41. Cryan JF, Lucki I (2000) Antidepressant-like behavioral effects mediated by 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther 295(3):1120–1126

    CAS  PubMed  Google Scholar 

  42. Tatarczynska E, Antkiewicz-Michaluk L, Klodzinska A, Stachowicz K, Chojnacka-Wojcik E (2005) Antidepressant-like effect of the selective 5-HT1B receptor agonist CP 94253: a possible mechanism of action. Eur J Pharmacol 516(1):46–50

    Article  CAS  PubMed  Google Scholar 

  43. Cremers TI, Rea K, Bosker FJ, Wikstrom HV, Hogg S, Mork A et al (2007) Augmentation of SSRI effects on serotonin by 5-HT2C antagonists: mechanistic studies. Neuropsychopharmacology 32(7):1550–1557

    Article  CAS  PubMed  Google Scholar 

  44. Bristow LJ, O’Connor D, Watts R, Duxon MS, Hutson PH (2000) Evidence for accelerated desensitisation of 5-HT2C receptors following combined treatment with fluoxetine and the 5-HT(1A) receptor antagonist, WAY 100,635, in the rat. Neuropharmacology 39(7):1222–1236

    Article  CAS  PubMed  Google Scholar 

  45. Nic Dhonnchadha BA, Ripoll N, Clenet F, Hascoet M, Bourin M (2005) Implication of 5-HT(2) receptor subtypes in the mechanism of action of antidepressants in the four plates test. Psychopharmacology 179(2):418–429

    Article  CAS  PubMed  Google Scholar 

  46. Diaz SL, Maroteaux L (2011) Implication of 5-HT2B receptors in the serotonin syndrome. Neuropharmacology 61:495–502

    Article  CAS  PubMed  Google Scholar 

  47. Urani A, Chourbaji S, Gass P (2005) Mutant mouse models of depression: candidate genes and current mouse lines. Neurosci Biobehav Rev 29(4-5):805–828

    Article  CAS  PubMed  Google Scholar 

  48. Dulawa SC, Holick KA, Gundersen B, Hen R (2004) Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 29(7):1321–1330

    Article  CAS  PubMed  Google Scholar 

  49. Tatarczynska E, Klodzinska A, Stachowicz K, Chojnacka-Wojcik E (2004) Effects of a selective 5-HT1B receptor agonist and antagonists in animal models of anxiety and depression. Behav Pharmacol 15(8):523–534

    Article  CAS  PubMed  Google Scholar 

  50. De Deurwaerdere P, Navailles S, Berg KA, Clarke WP, Spampinato U (2004) Constitutive activity of the serotonin2C receptor inhibits in vivo dopamine release in the rat striatum and nucleus accumbens. J Neurosci 24(13):3235–3241

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Launay JM, Schneider B, Loric S, Da Prada M, Kellermann O (2006) Serotonin transport and serotonin transporter-mediated antidepressant recognition are controlled by 5-HT2B receptor signaling in serotonergic neuronal cells. FASEB J 20:1843–1854

    Article  CAS  PubMed  Google Scholar 

  52. Popa D, Cerdan J, Reperant C, Guiard BP, Guilloux JP, David DJ et al (2010) A longitudinal study of 5-HT outflow during chronic fluoxetine treatment using a new technique of chronic microdialysis in a highly emotional mouse strain. Eur J Pharmacol 628(1-3):83–90

    Article  CAS  PubMed  Google Scholar 

  53. Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, Manta S et al (2007) Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55(5):712–725

    Article  CAS  PubMed  Google Scholar 

  54. Yamauchi M, Miyara T, Matsushima T, Imanishi T (2006) Desensitization of 5-HT2A receptor function by chronic administration of selective serotonin reuptake inhibitors. Brain Res 1067(1):164–169

    Article  CAS  PubMed  Google Scholar 

  55. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301(5634):805–809

    Article  CAS  PubMed  Google Scholar 

  56. Tanti A, Belzung C (2010) Open questions in current models of antidepressant action. Br J Pharmacol 159(6):1187–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. McDevitt RA, Neumaier JF (2011) Regulation of dorsal raphe nucleus function by serotonin autoreceptors: a behavioral perspective. J Chem Neuroanat 41(4):234–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Belmer A, Quentin E, Diaz SL, Guiard BP, Fernandez SP, Doly S et al (2018) Positive regulation of raphe serotonin neurons by serotonin 2B receptors. Neuropsychopharmacology 43:1623–1632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Verge D, Daval G, Patey A, Gozlan H, El Mestikawy S, Hamon M (1985) Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur J Pharmacol 113(3):463–464

    Article  CAS  PubMed  Google Scholar 

  60. Calizo LH, Akanwa A, Ma X, Pan Y-Z, Lemos JC, Craige C et al (2011) Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence. Neuropharmacology 61(3):524–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Andrade R, Haj-Dahmane S (2013) Serotonin neuron diversity in the dorsal raphe. ACS Chem Neurosci 4(1):22–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fernandez SP, Cauli B, Cabezas C, Muzerelle A, Poncer J-C, Gaspar P (2016) Multiscale single-cell analysis reveals unique phenotypes of raphe 5-HT neurons projecting to the forebrain. Brain Struct Funct 221(8):4007–4025

    Article  CAS  PubMed  Google Scholar 

  63. Bang SJ, Jensen P, Dymecki SM, Commons KG (2012) Projections and interconnections of genetically defined serotonin neurons in mice. Eur J Neurosci 35(1):85–96

    Article  PubMed  Google Scholar 

  64. Gaspar P, Lillesaar C (2012) Probing the diversity of serotonin neurons. Philos Trans R Soc Lond, B, Biol Sci 367(1601):2382–2394

    Article  CAS  Google Scholar 

  65. Altieri SC, Garcia-Garcia AL, Leonardo ED, Andrews AM (2013) Rethinking 5-HT1A receptors: emerging modes of inhibitory feedback of relevance to emotion-related behavior. ACS Chem Neurosci 4(1):72–83

    Article  CAS  PubMed  Google Scholar 

  66. Beck SG, Pan Y-Z, Akanwa AC, Kirby LG (2004) Median and dorsal raphe neurons are not electrophysiologically identical. J Neurophysiol 91(2):994–1005

    Article  PubMed  Google Scholar 

  67. Colgan LA, Putzier I, Levitan ES (2009) Activity-dependent vesicular monoamine transporter-mediated depletion of the nucleus supports somatic release by serotonin neurons. J Neurosci 29(50):15878–15887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Courtney NA, Ford CP (2016) Mechanisms of 5-HT1A receptor-mediated transmission in dorsal raphe serotonin neurons. J Physiol 594(4):953–965

    Article  CAS  PubMed  Google Scholar 

  69. Richardson-Jones JW, Craige CP, Guiard BP, Stephen A, Metzger KL, Kung HF et al (2010) 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron 65(1):40–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Janoshazi A, Deraet M, Callebert J, Setola V, Guenther S, Saubamea B et al (2007) Modified receptor internalization upon co-expression of 5-HT1B receptor and 5-HT2B receptors. Mol Pharmacol 71(6):1463–1474

    Article  CAS  PubMed  Google Scholar 

  71. Urban DJ, Zhu H, Marcinkiewcz CA, Michaelides M, Oshibuchi H, Rhea D et al (2016) Elucidation of the behavioral program and neuronal network encoded by dorsal raphe serotonergic neurons. Neuropsychopharmacology 41(5):1404–1415

    Article  CAS  PubMed  Google Scholar 

  72. Teissier A, Chemiakine A, Inbar B, Bagchi S, Ray RS, Palmiter RD et al (2015) Activity of Raphé serotonergic neurons controls emotional behaviors. Cell Rep 13(9):1965–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Colgan LA, Cavolo SL, Commons KG, Levitan ES (2012) Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites. J Neurosci 32(45):15737–15746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. De Kock CPJ, Cornelisse LN, Burnashev N, Lodder JC, Timmerman AJ, Couey JJ et al (2006) NMDA receptors trigger neurosecretion of 5-HT within dorsal raphe nucleus of the rat in the absence of action potential firing. J Physiol 577(Pt 3):891–905

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Holohean AM, Hackman JC (2004) Mechanisms intrinsic to 5-HT2B receptor-induced potentiation of NMDA receptor responses in frog motoneurones. Br J Pharmacol 143(3):351–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lee S, Jeong J, Kwak Y, Park SK (2010) Depression research: where are we now? Mol Brain 3:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23(5):238–245

    Article  CAS  PubMed  Google Scholar 

  78. Cryan JF, Holmes A (2005) The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 4(9):775–790

    Article  CAS  PubMed  Google Scholar 

  79. Diaz SL, Maroteaux L (2015) Dissecting a model of depressive-related phenotype and antidepressants effects in 129S2/SvPas mice. In: Blenau W, Baumann A (eds) Serotonin receptor technologies, Neuromethods, vol 95. Humana Press, Totowa, pp 59–82

    Chapter  Google Scholar 

  80. Diaz SL, Narboux-Nême N, Boutourlinsky K, Doly S, Maroteaux L (2016) Mice lacking the serotonin 5-HT2B receptor as an animal model of resistance to selective serotonin reuptake inhibitors antidepressants. Eur Neuropsychopharmacol 26(2):265–279

    Article  CAS  PubMed  Google Scholar 

  81. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20(24):9104–9110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Petrik D, Lagace DC, Eisch AJ (2012) The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Neuropharmacology 62(1):21–34

    Article  CAS  PubMed  Google Scholar 

  83. Hertz L, Rothman DL, Li B, Peng L (2015) Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift. Front Behav Neurosci 9:25

    PubMed  PubMed Central  Google Scholar 

  84. Banas SM, Diaz SL, Doly S, Belmer A, Maroteaux L (2015) Commentary: chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift. Front Behav Neurosci 9:207

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E et al (2003) Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci 23(1):349–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T et al (2004) Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci USA 101(29):10827–10832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sairanen M, Lucas G, Ernfors P, Castrén M, Castrén E (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25(5):1089–1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Deltheil T, Guiard BP, Cerdan J, David DJ, Tanaka KF, Reperant C et al (2008) Behavioral and serotonergic consequences of decreasing or increasing hippocampus brain-derived neurotrophic factor protein levels in mice. Neuropharmacology 55(6):1006–1014

    Article  CAS  PubMed  Google Scholar 

  89. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15(11):7539–7547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Russo-Neustadt AA, Alejandre H, Garcia C, Ivy AS, Chen MJ (2004) Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology 29(12):2189–2199

    Article  CAS  PubMed  Google Scholar 

  91. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9(4):519–525

    Article  CAS  PubMed  Google Scholar 

  92. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM (1997) Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 56(1):131–137

    Article  CAS  PubMed  Google Scholar 

  93. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22(8):3251–3261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ibarguen-Vargas Y, Surget A, Vourc’h P, Leman S, Andres CR, Gardier AM et al (2009) Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress. Behav Brain Res 202(2):245–251

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Investigadora CONICET, Instituto de Biologia Celular y Neurociencias Prof. E. De Robertis, IBCN, UBA-CONICET, Buenos Aires, Argentina

    Silvina L. Diaz

Authors
  1. Silvina L. Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Inserm, U1270, Institut du Fer a Moulin, Paris, France

    Luc Maroteaux

  2. Pharmacology, Strasbourg Medical school, Strasbourg, France

    Laurent Monassier

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Diaz, S.L. (2021). 5-HT2B Receptors and Antidepressants. In: Maroteaux, L., Monassier, L. (eds) 5-HT2B Receptors. The Receptors, vol 35. Springer, Cham. https://doi.org/10.1007/978-3-030-55920-5_21

Download citation

Publish with us

Policies and ethics

Search

Navigation