Skip to main content
SpringerLink
Log in

Cellular and Subcellular Localization of Serotonin Receptors in the Central Nervous System

  • Chapter
The Serotonin Receptors

Part of the book series: The Receptors ((REC))

Abstract

Immunocytochemistry allows for a precise localization of neurotransmitter receptors in tissues and cells. This review summarizes much of the available data on the cellular and subcellular distribution of serotonin (5-hydroxytryptamine [5-HT]) receptors in the mammalian central nervous system. Among fourteen 5-HT receptor types, all cloned and sequenced, only a few have yet been amenable to detailed immunocytochemical visualization, not only at the light microscopic but particularly at the electron microscopic level. The 5-HT1A and 5-HT2A receptors have been the most thoroughly investigated and provide a meaningful demonstration of the wealth of information to be gained from this methodological approach, not only in terms of anatomical and cytological localization, and thus physiological role and eventual implication in health and disease, but also of functional properties and drug effects.

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Leysen JE, Niemegeers CJE, Tollenaere JP, Laduron PM. Serotonergic component of neuroleptic receptors. Nature 1978;272:168–171.

    Article  PubMed  CAS  Google Scholar 

  2. Peroutka SG, Snyder SH. Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamine and [3H]spiroperidol. Mol Pharmacol 1979;16:687–699.

    PubMed  CAS  Google Scholar 

  3. Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 2002;71:533–554.

    Article  PubMed  CAS  Google Scholar 

  4. Beaudet A, Dournaud P, Boudin H. Complementarity of radioautographic and immunocytochemical techniques for localizing neuroreceptors at the light and electron microscopic level. Braz J Med Biol Res 1998;31:215–223.

    PubMed  CAS  Google Scholar 

  5. Chan J, Aoki C, Pickel VM. Optimization of differential immunogold-silver and peroxidase labeling with maintenance of ultrastructure in brain sections before plastic embedding. J Neurosci Methods 1990;33:113–127.

    Article  PubMed  CAS  Google Scholar 

  6. Novikoff AB, Novikoff PM, Quintana N, Davis C. Diffusion artifacts in 3,3′-diaminobenzidine cytochemistry. J Histochem Cytochem 1972;20:745–749.

    PubMed  CAS  Google Scholar 

  7. Bernard V, Somogyi P, Bolam JP. Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat. J Neurosci 1997;17:819–833.

    PubMed  CAS  Google Scholar 

  8. Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RJ. The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 1988;335:358–360.

    Article  PubMed  CAS  Google Scholar 

  9. Albert PR, Zhou QY, Van Tol HH, Bunzow JR, Civelli O. Cloning, functional expression and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. J Biol Chem 1990;265:5825–5832.

    PubMed  CAS  Google Scholar 

  10. Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M. Identification of presynaptic serotonin autoreceptors using anew ligand: 3H-PAT. Nature 1983;305:140–142.

    Article  PubMed  CAS  Google Scholar 

  11. Hall MD, El Mestikawy S, Emerit MB, Pichat L, Hamon M, Gozlan H. [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to pre-and postsynaptic 5-hydroxytryptamine sites in various regions of the rat brain. J Neurochem 1985;44:1685–1696.

    Article  PubMed  CAS  Google Scholar 

  12. Laporte A-M, Lima L, Gozlan H, Hamon M. Selective in vivo labelling of brain 5-HT 1A receptors by [3H]WAY 100635 in the mouse. Eur J Pharmacol 1994;27:505–514.

    Article  Google Scholar 

  13. Gozlan H, Thibault S, Laporte A-M, Lima L, Hamon M. The selective 5-HT1A antagonist radioligand [3H]WAY 100635 labels both G protein-coupled and free 5-HT1A receptors in rat brain membranes. Eur J Pharmacol 1995;288:173–186.

    Article  PubMed  CAS  Google Scholar 

  14. El Mestikawy S, Riad M, Laporte AM, et al. Production of specific anti-rat 5-HT1A receptor antibodies in rabbits injected with a synthetic peptide. Neurosci Lett 1990;118:189–192.

    Article  PubMed  Google Scholar 

  15. Riad M, El Mestikawy S, Vergé D, Gozlan H, Hamon M. Visualization and quantification of central 5-HT1A receptors with specific antibodies. Neurochem Int 1991;19:413–423.

    Article  CAS  Google Scholar 

  16. Raymond JR, Kim J, Beach RE, Tisher CC. Immunohistochemical mapping of cellular and subcellular distribution of 5-HT1A receptors in rat and human kidneys. Am J Physiol 1993;264:F9–F19.

    PubMed  CAS  Google Scholar 

  17. Verdot L, Bertin B, Guilloteau D, Strosberg AD, Hoebeke J. Characterization of pharmacologically active anti-peptide antibodies directed against the first and second extracellular loops of the serotonin 5-HT1A receptor. J Neurochem 1995;65:319–328.

    PubMed  CAS  Google Scholar 

  18. Azmitia EC, Gannon PJ, Kheck NM, Whitaker-Azmitia PM. Cellular localization of the 5-HT1A receptor in primate brain neurons and glial cells. Neuropsychopharmacology 1996;14:35–46.

    Article  PubMed  CAS  Google Scholar 

  19. Helke CJ, Capuano S, Tran N, Zhuo H. Immunocytochemical studies of the 5-HT(1A) receptor in ventral medullaryneurons that project to the intermediolateral cell column and contain serotonin or tyrosine hydroxylase immunoreactivity. J Comp Neurol 1997;379:261–270.

    Article  PubMed  CAS  Google Scholar 

  20. .Gérard C, Langlois X, Gingrich J, et al. Production and characterization of polyclonal antibodies recognizing the intracytoplasmic third loop of the 5-hydroxytryptamine1A receptor. Neuroscience 1994;62:721–739.

    Article  PubMed  Google Scholar 

  21. Zhou FC, Patel TD, Swartz D, Xu Y, Lin R, Kelley MR. Production and characterization of an anti-serotonin 1A receptor antibody which detects functional 5-HT1A binding sites. Mol Brain Res 1999;69:186–201.

    Article  PubMed  CAS  Google Scholar 

  22. Hartig PR. Molecular biology of 5-HT receptors. Trends Pharmacol Sci 1989;10:64–69.

    Article  PubMed  CAS  Google Scholar 

  23. Emerit MB, El Mestikawy S, Gozlan H, et al. Identification of the 5-HT1A receptor binding subunit in rat brain membranes using the photoaffinity probe [3H]-8-methoxy-2-[N-n-propyl,N-3-(2-nitro-4-azidophenyl)aminopropyl] aminotetraline. J Neurochem 1987;49:373–380.

    Article  PubMed  CAS  Google Scholar 

  24. Gozlan H, Ponchant M, Daval G, et al. 125I-Bolton-Hunter-8-methoxy-2-[N-propyl-N-propylamino]tetralin as a new selective radioligand of 5-HT1A sites in the rat brain. In vitro binding and autoradiographic studies. J Pharmacol Exp Ther 1988;244:751–759.

    PubMed  CAS  Google Scholar 

  25. Riad M, Garcia S, Watkins KC, et al. Somatodendritic localization of 5-HT1A and preterminal axonal localization of 5-HT 1B serotonin receptors in adult rat brain. J Comp Neurol 2000;417:181–194.

    Article  PubMed  CAS  Google Scholar 

  26. Kia HK, Miquel MC, Brisorgueil MJ, et al. Immunocytochemical localization of serotonin1A receptors in the rat central nervous system. J Comp Neurol 1996;365:289–305.

    Article  PubMed  CAS  Google Scholar 

  27. Sotelo C, Cholley B, El Mestikawy S, Gozlan H, Hamon M. Direct immunohistochemical evidence of the existance of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci 1990;2:1144–1154.

    Article  PubMed  Google Scholar 

  28. Miquel M-C, Doucet E, Boni C, et al. Central serotonin1A receptors: respective distributions of encoding mRNA, receptor protein and binding sites by in situ hybridization histochemistry, radioimmunohistochemistry and autoradiographic mapping in the rat brain. Neurochem Int 1991;19:453–465.

    Article  CAS  Google Scholar 

  29. Miquel M-C, Doucet E, Riad M, Adrien J, Vergé D, Hamon M. Effect of the selective lesion of serotoninergic neurons on the regional distribution of 5-HT1A receptor mRNA in the rat brain. Brain Res Mol Brain Res 1992;14:357–362.

    Article  PubMed  CAS  Google Scholar 

  30. Matthiessen L, Kia HK, Daval G, Riad M, Hamon M, Vergé D. Immunocytochemical localization of 5-HT1A receptors in the rat immature cerebellum. NeuroReport 1993;4:763–766.

    Article  PubMed  CAS  Google Scholar 

  31. Kia HK, Brisorgueil MJ, Hamon M, Calas A, Vergé D. Ultrastructural localization of 5-hydroxytryptamine1A receptors in the rat brain. J Neurosci Res 1996;46:697–708.

    Article  PubMed  CAS  Google Scholar 

  32. Riad M, Watkins KC, Doucet E, Hamon M, Descarries L. Agonist-induced internalization of serotonin-1A receptors in the dorsal raphe nucleus (autoreceptors) but not hippocampus (heteroreceptors). J Neurosci 2001;21:8378–8386.

    PubMed  CAS  Google Scholar 

  33. Riad M, Zimmer L, Rbah L, Watkins KC, Hamon M, Descarries L. Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18]MPPF in the nucleus raphe dorsalis of rat. J Neurosci 2004;24:5420–5426.

    Article  PubMed  CAS  Google Scholar 

  34. Zimmer L, Riad M, Rbah L, et al. Toward brain imaging of the internalization of serotonin 5-HT1A autoreceptors. NeuroImage 2004;22:1421–1426.

    Article  PubMed  CAS  Google Scholar 

  35. Blier P, de Montigny C. Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. Synapse 1987;1:470–480.

    Article  PubMed  CAS  Google Scholar 

  36. Blier P, de Montigny C. Electrophysiological investigation of the adaptive response of the 5-HT system to the administration of 5-HT1A receptor agonists. J Cardiovac Pharmacol 1990;15:S42–S48.

    Article  CAS  Google Scholar 

  37. Kennett GA, Marcou M, Dourisch CT, Curzon G. Single administration of 5-HT1A agonists decreases 5-HT1A presynaptic, but not postsynaptic receptormediated responses: relationship to antidepressant-like action. Eur J Pharmacol 1987;138:53–60.

    Article  PubMed  CAS  Google Scholar 

  38. Le Poul E, Boni C, Hanoun N, et al. Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine. Neuropharmacology 2000;39:110–122.

    Article  PubMed  Google Scholar 

  39. Voigt MM, Laurie DJ, Seeburg PH, Bach A. Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor. EMBO J 1991;10:4017–4023.

    PubMed  CAS  Google Scholar 

  40. Maroteaux L, Saudou F, Amlaiky N, Boschert U, Plassat JL, Hen R. Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Proc Natl Acad Sci USA 1992;89:3020–3024.

    Article  PubMed  CAS  Google Scholar 

  41. Adham N, Romanienko P, Hartig PR, Weinshank RL, Branchek T. The rat 5-hydroxytryptamine1B receptor is the species homologue of the human 5-hydroxytryptamine1D beta receptor. Mol Pharmacol 1992;41:1–7.

    PubMed  CAS  Google Scholar 

  42. Hamblin MW, Metcalf MA, McGuffin RW, Karpells S. Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity. Biochem Biophys Res Commun 1992;184:752–759.

    Article  PubMed  CAS  Google Scholar 

  43. Oksenberg D, Marsters SA, O’Dowd BF, et al. A single amino-acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors. Nature 1992;360:161–163.

    Article  PubMed  CAS  Google Scholar 

  44. Parker EM, Grisel DA, Iben LG, Shapiro RA. A single amino acid difference baccounts for the pharmacological distinctions between the rat and human 5-hydroxytryptamine1B receptors. J Neurochem 1993;60:380–383.

    Article  PubMed  CAS  Google Scholar 

  45. Hartig PR, Hoyer D, Humphrey PP, Martin GR. Alignment of receptor nomenclature with the human genome: classification of 5-HT1B and 5-HT1D receptor subtypes. Trends Pharmacol Sci 1996;17:103–105.

    Article  PubMed  CAS  Google Scholar 

  46. Boulenguez P, Segu L, Chauveau J, Morel A, Lanoir J, Delaage M. Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl[125I] iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites. J Neurochem 1992;58:951–959.

    Article  PubMed  CAS  Google Scholar 

  47. Bruinvels AT, Palacios JM, Hoyer D. Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn Schmiedebergs Arch Pharmacol 1993;347:569–582.

    Article  PubMed  CAS  Google Scholar 

  48. Boschert U, Amara DA, Segu L, Hen R. The mouse 5-hydroxytryptamine1B receptor is localized predominantly on axon terminals. Neuroscience 1994;58:167–182.

    Article  PubMed  CAS  Google Scholar 

  49. Doucet E, Pohl M, Fattaccini CM, Adrien J, El Mestikawy SE, Hamon M. In situ hybridization evidence for the synthesis of 5-HT1B receptor in serotoninergic neurons of anterior raphe nuclei in the rat brain. Synapse 1995;19:18–28.

    Article  PubMed  CAS  Google Scholar 

  50. Vergé D, Daval G, Marcinkiewicz M, et al. Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5,7-dihydroxytryptaminetreated rats. J Neurosci 1986;6:3474–3482.

    PubMed  Google Scholar 

  51. Sari Y, Miquel M-C, Brisorgueil MJ, et al. Cellular and subcellular localisation of 5-hydroxytryptamine1B receptors in the rat central nervous system: immunocytochemical, autoradiographic and lesion studies. Neuroscience 1999;88:899–915.

    Article  PubMed  CAS  Google Scholar 

  52. Boulenguez P, Pinard R, Segu L. Subcellular localization of 5-HT1B binding sites in the stratum griseum superficiale of the rat superior colliculus: an electron microscopic quantitative autoradiographic study. Synapse 1996;24:203–212.

    Article  PubMed  CAS  Google Scholar 

  53. Langlois X, Gerard C, Darmon M, Chauveau J, Hamon M, El Mestikawy S. Immunolabeling of central serotonin 5-HT1D beta receptors in the rat, mouse, and guinea pig with a specific anti-peptide antiserum. J Neurochem 1995;65:2671–2681.

    PubMed  CAS  Google Scholar 

  54. Sari Y, Lefèvre K, Bancila M, et al. Light and electron microscopic immunocytochemical visualization of 5-HT1B receptors in the rat brain. Brain Res 1997;760:281–286.

    Article  PubMed  CAS  Google Scholar 

  55. Riad M, Tong X-K, El Mestikawy S, Hamon M, Hamel E, Descarries L. Endothelial exprssion of the 5-hydroxytryptamine 1B antimigraine drug receptor in rat and human brain microvessels. Neuroscience 1998;86:1031–1035.

    Article  PubMed  CAS  Google Scholar 

  56. Elhusseiny A, Hamel E. 5-HT1 receptors in human and bovine intracortical microarteioles mediate both a constriction and a nitric oxide (NO)-dependent dilation. J Cereb Blood Flow Metab 1999;19(Suppl 1):S235.

    Google Scholar 

  57. Rapoport AM, Tepper SJ, Bigal ME, Sheftell FD. The triptan formulations: how to match patients and products. CNS Drugs 2003;17:431–447.

    Article  PubMed  CAS  Google Scholar 

  58. Pickard GE, Smith BN, Belenky M, Rea MA, Dudek FE, Sollars PJ. 5-HT1B receptor-mediated presynaptic inhibition of retinal input to the suprachiasmatic nucleus. J Neurosci 1999;19:4034–4045.

    PubMed  CAS  Google Scholar 

  59. Sleight AJ, Boess FG, Bös M, Bourson A. The putative 5-ht6 receptor: localization and function. Ann NY Acad Sci 1998;861:90–96.

    Article  Google Scholar 

  60. Auerbach SB, Rutter JJ, Juliano PJ. Substituted piperazine and indole compounds increase extracellular serotonin in rat diencephalon as determined by in vivo microdialysis. Neuropharmacology 1991;30:307–311.

    Article  PubMed  CAS  Google Scholar 

  61. Bosker FJ, van Esseveldt KE, Klompmakers AA, Westenberg HG. Chronic treatment with fluvoxamine by osmotic minipumps fails to induce persistent func tional changes in central 5-HT1A and 5-HT1B receptors, as measured by in vivo microdialysis in dorsal hippocampus of conscious rats. Psychopharmacology 1995;117:358–363.

    Article  PubMed  CAS  Google Scholar 

  62. Maura G, Raiteri M. Cholinergic terminals in rat hippocampus possess 5-HT1B receptors mediating inhibition of acetylcholine release. Eur J Pharmacol 1986;129:333–337.

    Article  PubMed  CAS  Google Scholar 

  63. Cassel JC, Jeltsch H, Neufang B, Lauth D, Szabo B, Jackisch R. Downregulation of muscarinic-and 5-HT1B-mediated modulation of [3H]acetylcholine release in hippocampal slices of rats with fimbria-fornix lesions and intrahippocampal grafts of septal origin. Brain Res 1995;704:153–166.

    Article  PubMed  CAS  Google Scholar 

  64. Sarhan H, Cloez-Tayarani I, Massot O, Fillion MP, Fillion G. 5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes. Naunyn Schmiedebergs Arch Pharmacol 1999;359:40–47.

    Article  PubMed  CAS  Google Scholar 

  65. Johnson SW, Mercuri NB, North RA. 5-Hydroxytryptamine1B receptors block the GABAB synaptic potential in rat dopamine neurons. J Neurosci 1992;12:2000–2006.

    PubMed  CAS  Google Scholar 

  66. Stanford IM, Lacey MG. Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors, on GABA-mediated synaptic input to rat substantia nigra pars reticulata neurons in vitro. J Neurosci 1996;16:7566–7573.

    PubMed  CAS  Google Scholar 

  67. Garlow SJ, Morilak DA, Dean RR, Roth BL, Ciaranello RD. Production and characterization of a specific 5-HT2 receptor antibody. Brain Res 1993;615:113–120.

    Article  PubMed  CAS  Google Scholar 

  68. Wu C, Yoder E, Shi L, et al. Development of monoclonal antibodies to the serotonin 5-HT2A receptor. Soc Neurosci Abstr 1995;21:1126.

    Google Scholar 

  69. Wu C, Yoder EJ, Shih J, et al. Development and characterization of monoclonal antibodies specific to the serotonin 5-HT2A receptor. J Histochem Cytochem 1998;46:811–824.

    PubMed  CAS  Google Scholar 

  70. Hamada S, Senzaki K, Hamaguchi-Hamada K, et al. Localization of 5-HT2A receptor in rat cerebral cortex and olfactory system revealed by immunocytochemistry using two antibodies raised in rabbit and chicken. Mol Brain Res 1998;54:199–211.

    Article  PubMed  CAS  Google Scholar 

  71. Roth BL, Palvimaki EP, Berry S, et al. 5-Hydroxytryptamine 2A (5-HT2A) receptor desensitization can occur without down-regulation. J Pharmacol Exp Ther 1995;275:1638–1646.

    PubMed  CAS  Google Scholar 

  72. Brownfield MS, Yracheta J, Chu F, Lorenz D, Diaz A. Functional chemical neuroanatomy of serotonergic neurons and their targets: antibody production and immunohistochemistry (IHC) for 5-HT, its precursor (5-HTP) and metabolite (5-HIAA) biosynthetic enzyme (TPH), transporter (SERT) and three receptors (5-HT2A, 5-HT5A, 5-HT7). Ann NY Acad Sci 1998;861:232–233.

    Article  PubMed  CAS  Google Scholar 

  73. Backstrom JR, Sanders-Bush E. Generation of anti-peptide antibodies against serotonin 5-HT2A and 5-HT2C receptors. J Neurosci Methods 1997;77:109–117.

    Article  PubMed  CAS  Google Scholar 

  74. Cornea-Hébert V, Watkins KC, Roth B, et al. Similar ultrastructural distribution of the 5-HT2A serotonin receptor and microtubule-associated protein MAP1 A in cortical dendrites of adult rat. Neuroscience 2002;113:23–35.

    Article  PubMed  Google Scholar 

  75. Morilak DA, Ciaranello RD. 5-HT2 receptor immunoreactivity on cholinergic neurons of the pontomesencephalic tegmentum shown by double immunofluorescence. Brain Res 1993;627:49–54.

    Article  PubMed  CAS  Google Scholar 

  76. Morilak DA, Garlow SJ, Ciaranello RD. Immunocytochemical localisation and description of neurons expressing serotonin2 receptors in the rat brain. Neuroscience 1993;54:701–717.

    Article  PubMed  CAS  Google Scholar 

  77. Morilak DA, Somogyi P, Lujan-Miras R, Ciaranello RD. Neurons expressing 5-HT2 receptors in the rat brain: neurochemical identification of cell types by immunocytochemistry. Neuropsychopharmacology 1994;11:157–166.

    Article  PubMed  CAS  Google Scholar 

  78. Willins DL, Deutch AY, Roth BL. Serotonin 5-HT2A receptors are expressed on pyramidal cells and interneurons in the rat cortex. Synapse 1997;27:79–82.

    Article  PubMed  CAS  Google Scholar 

  79. Jakab RL, Goldman-Rakic PS. 5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc Natl Acad Sci USA 1998;95:35–740.

    Article  Google Scholar 

  80. Cornea-Hébert V, Riad M, Wu C, Singh SK, Descarries L. Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat. J Comp Neurol 1999;409:187–209.

    Article  PubMed  Google Scholar 

  81. Maeshima T, Ito R, Hamada S, et al. The cellular localization of 5-HT2A receptors in the spinal cord and spinal ganglia of the adult rat. Brain Res 1998;797:118–124.

    Article  PubMed  Google Scholar 

  82. Maeshima T, Shutoh F, Hamada S, et al. Serotonin 2A receptor-like immunoreactivity in rat cerebellar Purkinje cells. Neurosci Lett 1998;252:72–74.

    Article  PubMed  CAS  Google Scholar 

  83. Geurts FJ, De Schutter E, Timmermans J-P. Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum. J Chem Neuroanat 2002;24:65–74.

    Article  PubMed  CAS  Google Scholar 

  84. Maeshima T, Shiga T, Ito R, Okado N. Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum. Neurosci Res 2004;50:411–417.

    Article  PubMed  CAS  Google Scholar 

  85. Fay R, Kubin L. Pontomedullary distribution of 5-HT2A receptor-like protein in the rat. J Comp Neurol 2000;418:323–345.

    Article  PubMed  CAS  Google Scholar 

  86. Xu T, Pandey SC. Cellular localization of serotonin2A (5-HT2A) receptors in the rat brain. Brain Res Bull 2000;51:499–505.

    Article  PubMed  CAS  Google Scholar 

  87. Moyer RW, Kennaway DJ. Immunohistochemical localization of serotonin receptors in the rat suprachiasmatic nucleus. Neurosci Lett 1999;271:147–150.

    Article  PubMed  CAS  Google Scholar 

  88. Griffiths JL, Lovick TA. Co-localization of 5-HT2A receptor-and GABA-immunoreactivity in neurones in the periaqueductal grey matter of the rat. Neurosci Lett 2002;326:151–154.

    Article  PubMed  CAS  Google Scholar 

  89. Nocjar C, Roth BL, Pehek EA. Localization of 5-HT2A receptors on dopamine cells in subnuclei of the midbrain A10 cell group. Neuroscience 2002;111:163–176.

    Article  PubMed  CAS  Google Scholar 

  90. Nosjean A, Hamon M, Darmon M. 5-HT2A receptors are expressed by catecholaminergic neurons in the rat nucleus tractus solitarii. NeuroReport 2002;13:2365–2369.

    Article  PubMed  CAS  Google Scholar 

  91. Yuan Q, Harley CW, McLean JH. Mitral cell beta1 and 5-HT2A receptor colocalization and cAMP coregulation: a new model of norepinephrine-induced learning in the olfactory bulb. Learn Mem 2003;10:5–15.

    Article  PubMed  Google Scholar 

  92. Luttgen M, Ove Ogren S, Meister B. Chemical identity of 5-HT2A receptor immunoreactive neurons of the rat septal complex and dorsal hippocampus. Brain Res 2004;1010:156–165.

    Article  PubMed  CAS  Google Scholar 

  93. Jakab RL, Goldman-Rakic PS. Segregation of serotonin 5-HT2A and 5-HT3 receptors in inhibitory circuits of the primate cerebral cortex. J Comp Neurol 2000;417:337–348.

    Article  PubMed  CAS  Google Scholar 

  94. Touri F, Welker E, Reiderer BM. Differential distribution of MAP1 A isoforms in the adult mouse barrel cortex and comparison with the serotonin 5-HT(2A) receptor. J Chem Neuroanat 2004;27:99–108.

    Article  PubMed  CAS  Google Scholar 

  95. Ikemoto K, Nishimura A, Okado N, Mikuni M, Nishi K, Nagatsu I. Human midbrain dopamine neurons express serotonin 2A receptor: an immunohistochemical demonstration. Brain Res 2000;853:377–380.

    Article  PubMed  CAS  Google Scholar 

  96. Eastwood SL, Burnet PWJ, Gittins R, Baker K, Harrison PJ. Expression of serotonin 5-HT2A receptors in the human cerebellum and alterations in schizophrenia. Synapse 2001;42:104–114.

    Article  PubMed  CAS  Google Scholar 

  97. Pandey GN, Dwivedi Y, Rizavi HS, et al. Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiatry 2002;159:419–429.

    Article  PubMed  Google Scholar 

  98. Bubser M, Backstrom JR, Sanders-Bush E, Roth BL, Deutch AY. Distribution of serotonin 5-HT2A receptors in afferents of the rat striatum. Synapse 2001;39:297–304.

    Article  PubMed  CAS  Google Scholar 

  99. Willins DL, Berry SA, Alsayegh L, et al. Clozapine and other 5-hydroxytryptamine-2A receptor antagonists alter the subcellular distribution of 5-hydroxytryptamine-2A receptors in vitro and in vivo. Neuroscience 1999;91:599–606.

    Article  PubMed  CAS  Google Scholar 

  100. Jansson A, Tinner B, Steinbusch HWM, Agnati LF, Fuxe K. On the relationship of 5-hydroxytryptamine neurons to 5-hydroxytryptamine 2A receptor-immunoreactive neuronal processes in the brain stem of rats. A double immunolabelling analysis. NeuroReport 1998;9:2505–2511.

    Article  PubMed  CAS  Google Scholar 

  101. Jansson A, Descarries L, Cornea-Hébert V, et al. Transmitter-receptor mismatches in central dopamine, serotonin, and neuropeptide systems. In: Walz W, ed., The neuronal environment: Brain homeostasis in health and disease. Totowa NJ: Humana, 2001; pp. 83–108.

    Google Scholar 

  102. Jansson A, Tinner B, Bancila M, et al. Relationships of 5-hydroxytryptamine immunoreactive terminal-like varicosities to 5-hydroxytryptamine-2A receptorimmunoreactive neuronal processes in the rat forebrain. J Chem Neuroanat 2001;22:185–203.

    Article  PubMed  CAS  Google Scholar 

  103. Descarries L, Beaudet A, Watkins KC. Serotonin nerve terminals in adult rat neocortex. Brain Res 1975;100:563–588.

    Article  PubMed  CAS  Google Scholar 

  104. Beaudet A, Descarries L. Quantitative data on serotonin nerve terminals in adult rat neocortex. Brain Res 1976;111:301–309.

    Article  PubMed  CAS  Google Scholar 

  105. Beaudet A, Descarries L. The monoamine innervation of rat cerebral cortex: synaptic and nonsynaptic axon terminals. Neuroscience 1978;3:851–860.

    Article  PubMed  CAS  Google Scholar 

  106. Li Q-H, Nakadate K, Tanaka-Nakadate S, Nakatsuka D, Cui Y, Watanabe Y. Unique expression patterns of 5-HT2A and 5-HT2C receptors in the rat brain during postnatal development: Western blot and immunohistochemical analysis. J Comp Neurol 2004;469:128–140.

    Article  PubMed  CAS  Google Scholar 

  107. Fischette CT, Nock B, Renner K. Effects of 5,7-dihydroxytryptamine on serotonin 1 and serotonin2 receptors throughout the rat central nervous system using quantitative autoradiography. Brain Res 1987;421:263–279.

    Article  PubMed  CAS  Google Scholar 

  108. Compan V, Segu L, Buhot MC, Daszuta A. Selective increases in serotonin 5-HT1B/1D and 5-HT2A/2C binding sites in adult rat basal ganglia following lesions of serotonergic neurons. Brain Res 1998;793:103–111.

    Article  PubMed  CAS  Google Scholar 

  109. Compan V, Segu L, Buhot MC, Daszuta A. Differential effects of serotonin (5-HT) lesions and synthesis blockade on neuropeptide-Y immunoreactivity and 5-HT1A, 5-HT1B/1D and 5-HT2A/2C receptor binding sites in the rat cerebral cortex. Brain Res 1998;795:264–276.

    Article  PubMed  CAS  Google Scholar 

  110. Mengod G, Pompeiano M, Martinez-Mir MI, Palacios JM. Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites. Brain Res 1990;524:139–143.

    Article  PubMed  CAS  Google Scholar 

  111. Pompeiano M, Palacios JM, Mengod G. Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Mol Brain Res 1994;23:163–178.

    Article  PubMed  CAS  Google Scholar 

  112. Wright DE, Seroogy KB, Lundgren KH, Davis BM, Jennes L. Comparative localization of serotonin 1A, 1C, and 2 receptor subtype mRNAs in rat brain. J Comp Neurol 1995;351:357–373.

    Article  PubMed  CAS  Google Scholar 

  113. Miner LAH, Backstrom JR, Sanders-Bush E, Sesack SR. Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex. Neuroscience 2003;116:107–117.

    Article  PubMed  CAS  Google Scholar 

  114. Doly S, Madeira A, Fischer J, et al. The 5-HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons. J Comp Neurol 2004;472:496–511.

    Article  PubMed  CAS  Google Scholar 

  115. Rodriguez JJ, Garcia DR, Pickel VM. Subcellular distribution of 5-hydroxytryptamine A and N-methyl-D-aspartate receptors within single neurons in rat motor and limbic striatum. J Comp Neurol 1999;413:219–231.

    Article  PubMed  CAS  Google Scholar 

  116. Doherty MD, Pickel VM. Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area. Brain Res 2000;864:176–185.

    Article  PubMed  CAS  Google Scholar 

  117. Rodriguez JJ, Doherty MD, Pickel VM. N-Methyl-D-aspartate (NMDA) receptors in the ventral tegmental area: subcellular distribution and colocalization with 5-hydroxytryptamine2A receptors. J Neurosci Res 2000;60:202–211.

    Article  PubMed  CAS  Google Scholar 

  118. Huang J, Pickel VM. Serotonin transporters (SERTs) within the rat nucleus of the solitary tract: subcellular distribution and relation to 5-HT2A receptors. J Neurocytol 2002;31:667–679.

    Article  PubMed  CAS  Google Scholar 

  119. Huang J, Pickel VM. Ultrastructural localization of serotonin2A and N-methyl-Daspartate receptors in somata and dendrites of single neurons within rat dorsal motor nulceus of the vagus. J Comp Neurol 2003;455:270–280.

    Article  PubMed  CAS  Google Scholar 

  120. Snowhill EW, Wamsley JK. Serotonin type-2 receptors undergo axonal transport in the medial forebrain bundle. Eur J Pharmacol 1983;95:325–327.

    Article  PubMed  CAS  Google Scholar 

  121. Tilakaratne N, Friedman E. Genomic responses to 5-HT1A or 5-HT2A/2C receptor activation is differentially regulated in four regions of rat brain. Eur J Pharmacol 1996;307:211–217.

    Article  PubMed  CAS  Google Scholar 

  122. Vaidya VA, Marek GJ, Aghajanian GK, Duman RS. 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J Neurosci 1997;17:2785–2795.

    PubMed  CAS  Google Scholar 

  123. Pei Q, Lewis L, Sprakes ME, Jones DG, Grahame-Smith DG, Zetterström TSC. Serotonergic regulation of mRNA expression of Arc, an immediate early gene selectively localized at neuronal dendrites. Neuropharmacology 2000;39:463–470.

    Article  PubMed  CAS  Google Scholar 

  124. Xia Z, Hufeisen SJ, Gray JA, Roth BL. The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro. Neuroscience 2003;122:907–920.

    Article  PubMed  CAS  Google Scholar 

  125. Kroeze WK, Willins DL, Roth BL. Proteins interacting with the third intracellular loop of human 5-HT2A serotonin receptors identified by yeast two-hybrid screening. Soc Neurosci Abstr 1999;25:1201.

    Google Scholar 

  126. Kroeze WK, Roth BL. Interaction of the third intracellular loop of the human 5-HT2A serotonin receptor with microtubule-associated protein 1A (MAP-1A). Soc Neurosci Abstr 2000;26:1426.

    Google Scholar 

  127. Choi D-S, Ward S, Messaddeq N, Launay J-M, Maroteaux L. 5-HT2B receptormediated serotonin morphogenetic functions in mouse cranial crest and myocardiac cells. Development 1997;124:1745–1755.

    PubMed  CAS  Google Scholar 

  128. Lauder JM, Wilkie MB, Wu C, Singh S. Expression of 5-HT2A, 5-HT2B and 5-HT2C receptors in the mouse embryo. Int J Dev Neurosci 2000;18:653–662.

    Article  PubMed  CAS  Google Scholar 

  129. Fiorica-Howells E, Hen R, Gingrich J, Li Z, Gershon MD. 5-HT2A receptors: location and functional analysis in intestines of wild-type and 5-HT2A knockout mice. Am J Physiol Gastrointest Liver Physiol 2002;282:G877–G893.

    PubMed  CAS  Google Scholar 

  130. Nebigil CG, Etienne N, Schaerlinger B, Hickel P, Launay JM, Maroteaux L. Developmentally regulated serotonin 5-HT2B receptors. Int J Dev Neurosci 2001;19:365–372.

    Article  PubMed  CAS  Google Scholar 

  131. Bonhaus DW, Bach C, DeSouza A, et al. The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol 1995;115:622–628.

    PubMed  CAS  Google Scholar 

  132. Choi D-S, Maroteaux L. Immunohistochemical localisation of the serotonin 5-HT2B receptor in mouse gut, cardiovascular system, and brain. FEBS Lett 1996;391:45–51.

    Article  PubMed  CAS  Google Scholar 

  133. Borman RA, Tilford NS, Harmer DW, et al. 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro. Br J Pharmacol 2002;135:1144–1151.

    Article  PubMed  CAS  Google Scholar 

  134. Launay JM, Herve P, Peoc’h K, et al. Functions of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med 2002;8:1129–1135.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  136. Flanigan TP, Reavley AC, Carey JE, Leslie RA. Evidence for expression of the 5-HT2B receptor mRNA in rat brain. Br J Pharm 1995;114:369P.

    Google Scholar 

  137. Bonaventure P, Guo H, Tian B, et al. Nuclei and subnuclei gene expression profiling in mammalian brain. Brain Res 2002;943:38–47.

    Article  PubMed  CAS  Google Scholar 

  138. Duxon MS, Flanigan TP, Reavley AC, Baxter GS, Blackburn TP, Fone KCF. Evidence for expression of the 5-hydroxytryptamine-2B receptor protein in the rat central nervous system. Neuroscience 1997;76:323–329.

    Article  PubMed  CAS  Google Scholar 

  139. Roth BL, Willins DL, Kristiansen K, Kroeze WK. 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptaminem2C):where structure meets function. Pharmacol Ther 1998;79:231–257.

    Article  PubMed  CAS  Google Scholar 

  140. Canton H, Emeson RB, Barker EL, et al. Identification, molecular cloning and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing. Mol Pharmacol 1996;50:799–807.

    PubMed  CAS  Google Scholar 

  141. Fitzgerald LW, Iyer G, Conklin DS, et al. Messenger RNA editing of the human serotonin 5-HT2C receptor. Neuropsychopharmacology 1999;21:82S–90S.

    PubMed  CAS  Google Scholar 

  142. Herrick-Davis K, Grinde E, Niswender CM. Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J Neurochem 1999;73:1711–1717.

    Article  PubMed  CAS  Google Scholar 

  143. Abramowski D, Rigo M, Duc D, Hoyer D, Staufenbiel M. Localization of the 5-hydroxytryptamine2C receptor protein in human and rat brain using specific antisera. Neuropharmacology 1995;34:1635–1645.

    Article  PubMed  CAS  Google Scholar 

  144. Clemett DA, Punhani T, Duxon MS, Blackburn TP, Fone KC. Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS. Neuropharmacology 2000;39:123–132.

    Article  PubMed  CAS  Google Scholar 

  145. Bancila M, Vergé D, Rampin O, et al. 5-Hydroxytryptamine2C receptors on spinal neurons controlling penile erection in the rat. Neuroscience 1999;92:1523–1537.

    Article  PubMed  CAS  Google Scholar 

  146. Bécamel C, Alonso G, Galéotti N, et al. Synaptic multiprotein complexes associated with 5-HT2C receptors: a proteomic approach. EMBO J 2002;21:2332–2342.

    Article  PubMed  Google Scholar 

  147. Bécamel C, Gavarini S, Chanrion B, et al. The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins. J Biol Chem 2004;279:20,257–20,266.

    Article  PubMed  CAS  Google Scholar 

  148. Peters JA, Malone HM, Lambert JJ. Recent advances in the electrophysiological characterization of 5-HT3 receptors. Trends Pharmacol Sci 1992;13:391–397.

    Article  PubMed  CAS  Google Scholar 

  149. Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5-HT3 receptor, a serotonin-gated ion channel. Science 1991;254:432–437.

    Article  PubMed  CAS  Google Scholar 

  150. Davies PA, Pistis M, Hanna MC, et al. The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 1999;397:359–363.

    Article  PubMed  CAS  Google Scholar 

  151. Hanna MC, Davies PA, Hales TG, Kirkness EF. Evidence for expression of heteromeric serotonin 5-HT3 receptors in rodents. J Neurochem 2000;75:240–247.

    Article  PubMed  CAS  Google Scholar 

  152. Dubin AE, Huvar R, D’Andrea MR, et al. The pharmacological and functional characteristics of the serotonin 5-HT3A receptor are specifically modified by a 5-HT3B receptor subunit. J Biol Chem 1999;274:30,799–30,810.

    Article  PubMed  CAS  Google Scholar 

  153. Férézou I, Cauli B, Hill EL, Rossier J, Hamel E, Lambolez B. 5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons. J Neurosci 2002;22:7389–7397.

    PubMed  Google Scholar 

  154. Sudweeks SN, Hooft JA, Yakel JL. Serotonin 5-HT3 receptors in rat CA1 hippocampal interneurons: functional and molecular characterization. J Physiol 2002;544:715–726.

    Article  PubMed  CAS  Google Scholar 

  155. Hope AG, Downie DL, Sutherland L, Lambert JJ, Peters JA, Burchell B. Cloning and functional expression of an apparent splice variant of the murine 5-HT3 receptor A subunit. Eur J Pharmacol 1993;245:187–192.

    Article  PubMed  CAS  Google Scholar 

  156. Werner P, Kawashima E, Reid J, et al. Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants. Brain Res Mol Brain Res 1994;26:233–241.

    Article  PubMed  CAS  Google Scholar 

  157. Miquel M-C, Emerit MB, Gingrich JA, Nosjean A, Hamon M, El Mestikawy S. Developmental changes in the differential expression of two serotonin 5-HT3 receptor splice variants in the rat. J Neurochem 1995;65:475–483.

    PubMed  CAS  Google Scholar 

  158. Brüss M, Eucker T, Göthert M, Bonisch H. Exon-intron organization of the human 5-HT3A receptor gene. Neuropharmacology 2000;39:308–315.

    Article  PubMed  Google Scholar 

  159. Doucet E, Miquel M-C, Nosjean A, Vergé D, Hamon M, Emerit MB. Immunolabeling of the rat central nervous system with antibodies partially selective of the short form of the 5-HT3 receptor. Neuroscience 2000;95:881–892.

    Article  PubMed  CAS  Google Scholar 

  160. Barnes JM, Barnes NM, Champaneria S, Costall B, Naylor RJ. Characterisation and autoradiographic localisation of 5-HT3 receptor recognition sites identified with [3H]-(S)-zacopride in the forebrain of the rat. Neuropharmacology 1990;29:1037–1045.

    Article  PubMed  CAS  Google Scholar 

  161. Laporte A-M, Koscielniak T, Ponchant M, Vergé D, Hamon M, Gozlan H. Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodozacopride and [3H]zacopride as radioligands. Synapse 1992;10:271–281.

    Article  PubMed  CAS  Google Scholar 

  162. Tecott LH, Maricq AV, Julius D. Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proc Natl Acad Sci USA 1993;90:1430–1434.

    Article  PubMed  CAS  Google Scholar 

  163. Martin KF, Hannon S, Phillips I, Heal DJ. Opposing roles for 5-HT1B and 5-HT3 receptors in the control of 5-HT release in rat hippocampus in vivo. Br J Pharmacol 1992;106:139–142.

    PubMed  CAS  Google Scholar 

  164. Haddjeri N, Blier P. Pre-and post-synaptic effects of the 5-HT3 agonist 2-methyl 5-HT on the 5-HT system in the rat brain. Synapse 1995;20:54–67.

    Article  PubMed  CAS  Google Scholar 

  165. Bagdy E, Solyom S, Harsing LG. Feedback stimulation of somatodendritic serotonin release: a 5-HT3 receptor-mediated effect in the raphé nuclei of the rat. Brain Res Bull 1998;45:203–208.

    Article  PubMed  CAS  Google Scholar 

  166. Carboni E, Acquas E, Frau R, Di Chiara G. Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 1989;164:515–519.

    Article  PubMed  CAS  Google Scholar 

  167. Imperato A, Angelucci L. 5-HT3 receptors control dopamine release in the nucleus accumbens of freely moving rats. Neurosci Lett 1989;101:214–217.

    Article  PubMed  CAS  Google Scholar 

  168. Chen JP, van Praag HM, Gardner EL. Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens. Brain Res 1991;543:354–357.

    Article  PubMed  CAS  Google Scholar 

  169. Ashworth-Preece MA, Jarrott B, Lawrence AJ. 5-Hydroxytryptamine3 receptor modulation of excitatory amino acid release in the rat nucleus tractus solitarius. NeurosciLett 1995;191:75–78.

    CAS  Google Scholar 

  170. Wang Y, Ramage AG, Jordan D. Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal preganglionic neurones in anaesthetized rats. J Physiol 1998;509:683–694.

    Article  PubMed  CAS  Google Scholar 

  171. Consolo S, Bertorelli R, Russi G, Zambelli M, Ladinsky H. Serotonergic facilitation of acetylcholine release in vivo from rat dorsal hippocampus via serotonin 5-HT3 receptors. J Neurochem 1994;62:2254–2261.

    PubMed  CAS  Google Scholar 

  172. Ropert N, Guy N. Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro. J Physiol 1991;441:121–136.

    PubMed  CAS  Google Scholar 

  173. Turton S, Gillard NP, Stephenson FA, McKernan RM. Antibodies against the 5-HT3-A receptor identify a 54 kDa protein affinity-purified from NCB20 cells. Mol Neuropharmacol 1993;3:167–171.

    CAS  Google Scholar 

  174. Kia HK, Miquel M-C, McKernan RM, et al. Localization of 5-HT3 receptors in the rat spinal cord: immunohistochemistry and in situ hybridization. NeuroReport 1995;6:257–261.

    Article  PubMed  CAS  Google Scholar 

  175. Morales M, Battenberg E, de Lecea L, Sanna PP, Bloom FE. Cellular and subcellular immunolocalization of the type 3 serotonin receptor in the rat central nervous system. Mol Brain Res 1996;36:251–260.

    Article  PubMed  CAS  Google Scholar 

  176. Morales M, De Battenberg E, Bloom FE. Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord. J Comp Neurol 1998;402:385–401.

    Article  PubMed  CAS  Google Scholar 

  177. Morales M, Battenberg E, de Lecea L, Bloom FE. The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus. Brain Res 1996;731:199–202.

    Article  PubMed  CAS  Google Scholar 

  178. Morales M, Bloom FE. The 5-HT3 receptor is present in different subpopulations of GABAergic neurons in the rat telencephalon. J Neurosci 1997;17:3157–3167.

    PubMed  CAS  Google Scholar 

  179. Spier AD, Wotherspoon G, Nayak SV, Nichols RA, Priestley JV, Lummis SC. Antibodies against the extracellular domain of the 5-HT3 receptor label both native and recombinant receptors. Brain Res Mol Brain Res 1999;67:221–230.

    Article  PubMed  CAS  Google Scholar 

  180. Huang J, Spier AD, Pickel VM. 5-HT3A receptor subunits in the rat medial nucleus of the solitary tract: subcellular distribution and relation to the serotonin transporter. Brain Res 2004;1028:156–169.

    Article  PubMed  CAS  Google Scholar 

  181. Hamon M, Gallissot MC, Ménard F, Gozlan H, Bourgoin S, Vergé D. 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol 1989;164:315–322.

    Article  PubMed  CAS  Google Scholar 

  182. Hewlett WA, Trivedi BL, Zhang ZJ, et al. Characterization of (S)-des-4-amino-3-[125I]iodozacopride ([125I]DAIZAC), a selective high-affinity radioligand for 5-hydroxytryptamine3 receptors. J Pharmacol Exp Ther 1999;288:221–231.

    PubMed  CAS  Google Scholar 

  183. Miquel M-C, Emerit MB, Nosjean A, et al. Differential subcellular localization of the 5-HT3-As receptor subunit in the rat central nervous system. Eur J Neurosci 2002;15:449–457.

    Article  PubMed  Google Scholar 

  184. Dumuis A, Bouhelal R, Sebben M, Cory R, Bockaert J. A nonclassical 5-hydroxytry ptamine receptor positively coupled with adenylate cyclase in the central ner vous system. Mol Pharmacol 1988;34:880–887.

    PubMed  CAS  Google Scholar 

  185. Gerald C, Adham N, Kao HT, et al. The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J 1995;14:2806–2815.

    PubMed  CAS  Google Scholar 

  186. Claeysen S, Sebben M, Journot L, Bockaert J, Dumius A. Cloning, expression and pharmacology of the mouse 5-HT(4L) receptor. FEBS Lett 1996;398:19–25.

    Article  PubMed  CAS  Google Scholar 

  187. Claeysen S, Faye P, Sebben M, Taviaux S, Bockaert J, Dumius A. 5-HT4 receptors: cloning and expression of new splice variants. Ann NY Acad Sci 1998;861:49–56.

    Article  PubMed  CAS  Google Scholar 

  188. Claeysen S, Sebben M, Becamel C, Bockaert J, Dumius A. Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain. Mol Pharmacol 1999;55:910–920.

    PubMed  CAS  Google Scholar 

  189. Bender E, Pindon A, van Oers I, et al. Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant. J Neurochem 2000;74:478–489.

    Article  PubMed  CAS  Google Scholar 

  190. Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R. Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in carboxyl terminus. J Neurochem 1998;70:2252–2261.

    PubMed  CAS  Google Scholar 

  191. Vilaró MT, Doménech T, Palacios JM, Mengod G. Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants. Neuropharmacology 2002;42:60–73.

    Article  PubMed  Google Scholar 

  192. Bockaert J, Claeysen S, Compan V, Dumuis A. 5-HT4 receptors. Curr Drug Targets: CNS Neurol Disord 2004;3:39–51.

    Article  CAS  Google Scholar 

  193. Brattelid T, Kvingedal AM, Krobert KA, et al. Cloning, pharmacological characterization and tissue distribution of a novel 5-HT4 receptor splice variant, 5-HT4(i). Naunyn Schmiedebergs Arch Pharmacol 2004;369:616–628.

    Article  PubMed  CAS  Google Scholar 

  194. Waeber C, Sebben M, Nieoullon A, Bockaert J, Dumuis A. Regional distribution and ontogeny of 5-HT4 binding sites in rodent brain. Neuropharmacology 1994;33:527–541.

    Article  PubMed  CAS  Google Scholar 

  195. Reynolds GP, Mason SL, Meldrum A, et al. 5-Hydroxytryptamine (5-HT)4 receptors in post mortem human brain tissue: distribution, pharmacology and effects of neurodegenerative diseases. Brit J Pharmacol 1995;114:993–998.

    CAS  Google Scholar 

  196. Varnas K, Halldin C, Pike VW, Hall H. Distribution of 5-HT4 receptors in the postmortem human brain: an autoradiographic study using [125I]SB 207710. Eur Neuropsychopharmacol 2003;13:228–234.

    Article  PubMed  CAS  Google Scholar 

  197. Jakeman LB, To ZP, Eglen RM, Wong EH, Bonhaus DW. Quantitative autoradiography of 5-HT4 receptors in brains of three species using two structurally distinct radioligands, [3H]GR113808 and [3H]BIMU-1. Neuropharmacology 1994;33:1027–1038.

    Article  PubMed  CAS  Google Scholar 

  198. Vilaró MT, Cortes R, Gerald C, Branchek TA, Palacios JM, Mengod G. Localization of 5-HT4 receptor mRNA in rat brain by in situ hybridization histochemistry. Brain Res Mol Brain Res 1996;43:356–360.

    Article  PubMed  Google Scholar 

  199. Bonaventure P, Hall H, Gommeren W, et al. Mapping of serotonin 5-HT(4) receptor mRNA and ligand binding sites in the post-mortem human brain. Synapse 2000;36:35–46.

    Article  PubMed  CAS  Google Scholar 

  200. Patel S, Roberts J, Moorman J, Reavill C. Localization of serotonin-4 receptors in the striatonigral pathway in rat brain. Neuroscience 1995;69:1159–1167.

    Article  PubMed  CAS  Google Scholar 

  201. Compan V, Daszuta A, Salin P, Sebben M, Bockaert J, Dumuis A. Lesion study of the distribution of serotonin 5-HT4 receptors in rat basal ganglia and hippocampus. Eur J Neurosci 1996;8:2591–2598.

    Article  PubMed  CAS  Google Scholar 

  202. Lucas G, Debonnel G. 5-HT4 receptors exert a frequency-related facilitatory control on dorsal raphe nucleus 5-HT neuronal activity. Eur J Neurosci 2002;16:817–822.

    Article  PubMed  Google Scholar 

  203. Nelson DL. 5-HT5 receptors. Curr Drug Targets: CNS Neurol Disord 2004;3:53–58.

    Article  CAS  Google Scholar 

  204. Erlander MG, Lovenberg TW, Baron BM, et al. Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain. Proc Natl Acad Sci USA 1993;90:3452–3456.

    Article  PubMed  CAS  Google Scholar 

  205. Matthes H, Boschert U, Amlaiky N, et al. Mouse 5-hydroxytryptamine5A and5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Mol Pharmacol 1993;43:313–319.

    PubMed  CAS  Google Scholar 

  206. Rees S, Den D, Foord S, et al. Cloning and characterization of the human 5-HT(5A) serotonin receptor. FEBS Lett 1994;335:242–246.

    Article  Google Scholar 

  207. Grailhe R, Grabtree GW, Hen R. Human 5-HT(5) receptors: the 5-HT(5A) rec eptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution. Eur J Pharmacol 2001;418:157–167.

    Article  PubMed  CAS  Google Scholar 

  208. Wang ZY, Keith IM, Beckman MJ, Brownfield MS, Vidruk EH, Bisgard GE. 5-HT5A receptors in the carotid body chemoreception pathway of rat. Neurosci Lett 2000;278:9–12.

    Article  PubMed  CAS  Google Scholar 

  209. Oliver KR, Kinsey AM, Wainwright A, Sirinathsinghji DJS. Localization of 5-ht5A receptor-like immunoreactivity in the rat brain. Brain Res 2000;867:131–142.

    Article  PubMed  CAS  Google Scholar 

  210. Kinsey AM, Wainwright A, Heavens R, Sirinathsinghji DJS, Oliver KR. Distribution of 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 receptor mRNAs in the rat brain. Mol Brain Res 2001;88:194–198.

    Article  PubMed  CAS  Google Scholar 

  211. Duncan MJ, Jennes L, Jefferson JB, Brownfield MS. Localization of serotonin5A receptors in discrete regions of the circadian timing system in the Syrian hamster. Brain Res 2000;869:178–185.

    Article  PubMed  CAS  Google Scholar 

  212. Rea MA, Pickard GE. Serotonergic modulation of photic entrainment in the Syrian hamster. Biol Rhythm Res 2000;31:284–314.

    Article  CAS  Google Scholar 

  213. Kennaway DJ, Moyer RW. Serotonin 5-HT2C agonists mimic the effect of light pulses on circadian rhythms. Brain Res 1998;806:257–279.

    Article  PubMed  CAS  Google Scholar 

  214. Sprouse J, Reynolds L, Braselton J, Schmidt A. Serotonin-induced phase advances of SCN neuronal firing in vitro: a possibole role for 5-HT5A receptors. Synapse 2004;54:111–118.

    Article  PubMed  CAS  Google Scholar 

  215. Doly S, Fischer J, Brisorgueil M-J, Vergé D, Conrath M. 5-HT5A receptor localization in the rat spinal cord suggests a role in nociception and control of pelvic floor musculature. J Comp Neurol 2004;476:316–329.

    Article  PubMed  CAS  Google Scholar 

  216. Ramage AG. Identification of one of the least well understood 5-HT receptors (5-Ht5A) in the spinal cord. J Comp Neurol 2004;476:313–315.

    Article  PubMed  CAS  Google Scholar 

  217. Serrats J, Raurich A, Vilaró MT, Mengod G, Cortes R. 5-ht5B receptor mRNA in the raphe nuclei: coexpression with serotonin transporter. Synapse 2004;51:102–111.

    Article  PubMed  CAS  Google Scholar 

  218. Monsma Jr FJ, Shen Y, Ward RP, Hamblin MW, Sibley DR. Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 1993;43:320–327.

    PubMed  CAS  Google Scholar 

  219. Ruat M, Traiffort E, Arrang JM, et al. A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation. Biochem Biophys Res Commun 1993;193:268–276.

    Article  PubMed  CAS  Google Scholar 

  220. Ward RP, Hamblin MW, Lachowicz JE, Hoffman BJ, Sibley DR, Dorsa DM. Localization of serotonin subtype 6 receptor messenger mRNA in the rat brain by in situ hybridization histochemistry. Neuroscience 1995;64:1105-1011.

    Google Scholar 

  221. Ward RP, Dorsa DM. Colocalization of serotonin receptor subtypes 5-HT2A, 5-HT2C, and 5-HT6 with neuropeptides in rat striatum. J Comp Neurol 1996;370:405–414.

    Article  PubMed  CAS  Google Scholar 

  222. Gérard C, El Mestikawy S, Lebrand C, et al. Quantitative RT-PCR distribution of serotonin 5-HT6 receptor mRNA in the central nervous system of control or 5, 7-dihydroxytryptamine-treatedrats. Synapse 1996;23:164–173.

    Article  PubMed  Google Scholar 

  223. Gérard C, Martres M-P, Lefèvre K, et al. Immuno-localization of serotonin 5-HT6 receptor-like material in the rat central nervous system. Brain Res 1997;746:207–219.

    Article  PubMed  Google Scholar 

  224. Hamon M, Doucet E, Lefèvre K, et al. Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors. Neuropsychopharmacology 1999;21:68S–76S.

    PubMed  CAS  Google Scholar 

  225. Brailov I, Bancila M, Brisorgueil M-J, Miquel M-C, Hamon M, Vergé D. Localization of 5-HT6 receptors at the plasma membrane of neuronal cilia in the rat brain. Brain Res 2000;872:271–275.

    Article  PubMed  CAS  Google Scholar 

  226. Roth BL, Craigo SC, Choudhary MS, et al. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther 1994;268:1403–1410.

    PubMed  CAS  Google Scholar 

  227. Sleight AJ, Smith RJ, Marsden CA, Palfreyman MG. The effects of chronic treatment with amitriptyline and MDL 72394 on the control of 5-HT release in vivo. Neuropharmacology 1989;28:477–480.

    Article  PubMed  CAS  Google Scholar 

  228. Branchek TA, Blackburn TP. 5-HT6 receptors as emerging targets for drug discovery. Annu Rev Pharmacol Toxicol 2000;40:319–334.

    Article  PubMed  CAS  Google Scholar 

  229. Bard JA, Zgombick J, Adham N, Vaysse P, Brancheck TA, Weinshank RL. Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem 1993;268:23,422–23,426.

    PubMed  CAS  Google Scholar 

  230. Lovenberg TW, Baron BM, de Lecea L, et al. A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 1993;11:449–458.

    Article  PubMed  CAS  Google Scholar 

  231. Ruat M, Traiffort E, Leurs R, et al. Molecular cloning, characterization, and localization of a high affinity serotonin receptor (5-HT7) activating cAMP formation. Proc Natl Acad Sci USA 1993;90:8547–8551.

    Article  PubMed  CAS  Google Scholar 

  232. Shen Y, Monsma J FJ Jr, Metcalf MA, Jose PA, Hamblin MW, Sibley DR. Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem 1993;268:18,200–18,204.

    PubMed  CAS  Google Scholar 

  233. Tsou AP, Kosaka A, Bach C, et al. Cloning and expression of a 5-hydroxytryptamine 7 receptor positively coupled to adenylyl cyclase. J Neurochem 1994;63:456–464.

    PubMed  CAS  Google Scholar 

  234. Heidmann DE, Metcalf MA, Kohen R, Hamblin MW. Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: species differences due to altered intron-exon organization. J Neurochem 1997;68:1372–1381.

    Article  PubMed  CAS  Google Scholar 

  235. Heidmann DE, Szot P, Kohen R, Hamblin MW. Function and distribution of three rat 5-hydroxytryptamine7 (5-HT7) receptor isoforms produced by alternative splicing. Neuropharmacology 1998;37:1621–1632.

    Article  PubMed  CAS  Google Scholar 

  236. Krobert KA, Bach T, Syversvsveen T, Kvingedal AM, Levy FO. The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution. Naunyn Schmiedebergs Arch Pharmacol 2001;363:620–632.

    Article  PubMed  CAS  Google Scholar 

  237. Gustafson EL, Durkin MM, Bard JA, Zgombick J, Branchek TA. A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5-ht7 receptor in rat brain. Br J Pharmacol 1996;117:657–666.

    PubMed  CAS  Google Scholar 

  238. Mengod G, Vilaro MT, Raurich A, Lopez-Gimenez JF, Cortes R, Palacios JM. 5-HT receptors in mammalian brain: receptor autoradiography and in situ hybridization studies of new ligands and newly identified receptors. Histochem J 1996;28:747–758.

    Article  PubMed  CAS  Google Scholar 

  239. Neumaier JF, Sexton TJ, Yracheta J, Diaz AM, Brownfield M. Localization of 5-HT7 receptors in rat brain by immunocytochemistry, in situ hybridization, and agonist-stimulated cFos expression. J Chem Neuroanat 2001;21:63–73.

    Article  PubMed  CAS  Google Scholar 

  240. Bickmeyer U, Heine M, Manzke T, Richter DW. Differential modulation of Ih by 5-HT receptors in mouse CA1 hippocampal neurons. Eur J Neurosci 2002;16:209–218.

    Article  PubMed  Google Scholar 

  241. Muneoka KT, Takigawa M. 5-Hydroxytryptamine7 (5-HT7) receptor immunoreactivity-positive’ stigmoid body’-like structure in developing rat brains. Int Dev Neurosci 2003;21:133–143.

    Article  CAS  Google Scholar 

  242. Belenky MA, Pickard GE. Subcellular distribution of 5-HT1B and 5-HT7 receptors in the mouse suprachiasmatic nucleus. J Comp Neurol 2001;432:371–388.

    Article  PubMed  CAS  Google Scholar 

  243. Hedlund PB, Sutcliffe JG. Functional, molecular and pharmacological advances in 5-HT7 receptor research. Trends Pharmacol Sci 2004;25:481–486.

    Article  PubMed  CAS  Google Scholar 

  244. Roth BL. Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry 1994;6:67–78.

    Article  PubMed  CAS  Google Scholar 

  245. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology 1999;38:1083–1152.

    Article  PubMed  CAS  Google Scholar 

  246. Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 2003;4:1002–1012.

    Article  PubMed  CAS  Google Scholar 

  247. Jordan BA, Devi LA. G protein-coupled receptor heterodimerization modulates receptor function. Nature 1999;399:697–700.

    Article  PubMed  CAS  Google Scholar 

  248. Bouvier M. Oligomerization of G protein-coupled transmitter receptors. Nat Rev Neurosci 2001;2:274–286.

    Article  PubMed  CAS  Google Scholar 

  249. Xie Z, Lee SP, O’Dowd BF, George SR. Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett 1999;456:63–67.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology and Cell Biology and of Physiology, Faculty of Medicine, Université de Montréal, Montréal, (QC), Canada

    Laurent Descarries, Virginia Cornea-Hébert & Mustapha Riad

Authors
  1. Laurent Descarries
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virginia Cornea-Hébert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mustapha Riad
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biochemistry, Case Western Reserve University-School of Medicine, Cleveland, OH

    Bryan L. Roth MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Descarries, L., Cornea-Hébert, V., Riad, M. (2006). Cellular and Subcellular Localization of Serotonin Receptors in the Central Nervous System. In: Roth, B.L. (eds) The Serotonin Receptors. The Receptors. Humana Press. https://doi.org/10.1007/978-1-59745-080-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-080-5_9

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-568-2

  • Online ISBN: 978-1-59745-080-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation