Skip to main content
SpringerLink
Log in

Effect of the selective activation of serotonin 5-HT3 receptors on sleep and waking

  • Chapter
Serotonin and Sleep: Molecular, Functional and Clinical Aspects

Abstract

The 5-HT3 receptor is a ligand-gated ion channel that belongs to the Cys-loop family, which also includes receptors such as the nicotinic acetylcholine receptor. As other 5-HT receptors subtypes, the 5-HT3 receptor seems to be involved in a large range of physiological processes, among of them sleep. Its role in the sleep-wake physiology has not been clearly established until now, but several pieces of evidence show its activation effect on wakefulness and inhibitory effect on slow-wave sleep. In addition, the 5-HT3 receptors seem to be implicated in circadian rhythm regulation and in REM sleep propensity. Many studies highlight its role in sleep disorders and more precisely in obstructive sleep apnea (OSA) and in fibromyalgia. Its effects in OSA are double. Indeed, 5-HT3 receptor antagonists increase respiration both at the central and the peripheral levels, and thus are potential therapeutic drugs for OSA. Drugs acting on 5-HT transmission have brought interesting results in animal models of apnea syndrome, as well as in patients with OSA. However, results are still disappointing since, in contrast to nasal continuous positive airway pressure that suppress nearly all respiratory events, drugs only lower the respiratory disturbance index by about 20–50%. Chronic pain that relates to inflammatory processes implicates 5-HT3 neurotransmission, and there is some evidence that the 5-HT3 receptor antagonist tropisetron had beneficial effects on pain intensity and sleep disturbance in patients with fibromyalgia.

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
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. Färber L, Drechsler S, Ladenburger S Gschaidmeier H, Fischer W (2007) The neuronal 5-HT3 receptor network after 20 years of research. Evolving concepts in management of pain and inflammation. Eur J Pharmacol 560: 1–8

    Google Scholar 

  2. Eisensamer B, Uhr M, Meyr S Gimpl G, Deiml T, Rammes G, Lambert JJ, Zieglgansberger W, Holsboer F, Rupprecht R (2005) Antidepressant and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains. J Neurosci 25: 10198–10206

    PubMed  CAS  Google Scholar 

  3. Lecrubier Y, Puech AJ, Azcona A, Bailey PE, Lataste X (1993) A randomized doubleblind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology 112: 129–133

    PubMed  CAS  Google Scholar 

  4. McGinty DJ, Sterman MB (1968) Sleep suppression after basal forebrain lesion the cat. Science 160: 1235–1255

    Google Scholar 

  5. Jouvet M (1969) Biogenic amines and the states of sleep. Science 163: 32–41

    PubMed  CAS  Google Scholar 

  6. Koella WP (1969) Serotonin and sleep. Exp Med Surg 27: 157–169

    PubMed  CAS  Google Scholar 

  7. McGinty DJ, Harper RM (1976) Dorsal raphe neurones: depression of firing during sleep in cats. Brain Res 101: 569–575

    PubMed  CAS  Google Scholar 

  8. Cespuglio R, Faradji H, Guidon G, Jouvet M (1984) Voltametric detection of brain 5-hydroxyindolamines: A new technology applied to sleep research. Exp Brain Res 8: 95–105

    CAS  Google Scholar 

  9. Adrien J, Tissier MH, Lanfumey L, Haj-Dahmane S, Jolas T, Franc B, Hamon M (1992) Central action of 5-HT3 receptor ligands in the regulation of sleep-wakefulness and raphe neuronal activity in the rat. Neuropharmacology 31: 519–529

    PubMed  CAS  Google Scholar 

  10. Ponzoni A, Monti JM, Jantos H (1993) The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat. Eur J Pharmacol 249: 259–264

    PubMed  CAS  Google Scholar 

  11. Ponzoni A, Monti JM, Jantos H, Altier H, Monti D (1995) Increased waking after intra-accumbens injection of m-chlorophenylbiguanide: Prevention with serotonin or dopamine receptor antagonists. Eur J Pharmacol 278: 111–115

    PubMed  CAS  Google Scholar 

  12. Rothe B, Guldner J, Hohlfeldt E, Lauer CJ, Pollmacher T, Holsboer F, Steiger A (1994) Effects of 5HT3 receptor antagonism by tropisetron on the sleep EEG and on nocturnal hormone secretion. Neuropsychopharmacology 11: 101–106

    PubMed  CAS  Google Scholar 

  13. Staner L, Linker T, Toussaint M, Danjou P, Roegel JC, Luthringer R, Le Fur G, Macher JP (2001) Effects of the selective activation of 5-HT3 receptors on sleep: a polysomnographic study in healthy volunteers. Eur Neuropsychopharmacol 11: 301–305

    PubMed  CAS  Google Scholar 

  14. Veasey SC (2003) Serotonin agonists and antagonists in obstructive sleep apnea: Therapeutic potential. Am J Respir Med 2: 21–29

    PubMed  CAS  Google Scholar 

  15. Boess FG, Beroukhim R, Martin IL (1995) Ultrastructure of the 5-hydroxytryptamine3 receptor. J Neurochem 64: 1401–1405

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  17. Corringer PJ, Le Novère N, Changeux JP (2000) Nicotinic receptors at the amino acid level. Annu Rev Pharmacol Toxicol 40: 431–458

    PubMed  CAS  Google Scholar 

  18. Boess FG, Steward LJ, Steele JA, Liu D, Reid J, Glencorse TA, Martin IL (1997) Analysis of the ligand binding site of the 5-HT3 receptor using site directed mutagenesis: importance of glutamate 106. Neuropharmacology 36: 637–647

    PubMed  CAS  Google Scholar 

  19. Mochizuki S, Miyake A, Furuichi K (1999) Identification of a domain affecting agonist potency of meta-chlorophenylbiguanide in 5-HT3 receptors. Eur J Pharmacol 369: 125–132

    PubMed  CAS  Google Scholar 

  20. Spier AD, Lummis SC (2000) The role of tryptophan residues in the 5-hydroxytryptamine(3) receptor ligand binding domain. J Biol Chem 275: 5620–5625

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  23. Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, Hales TG, Kirkness EF (1999) The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 397: 359–363

    PubMed  CAS  Google Scholar 

  24. Dubin AE, Huvar R, D’Andrea MR, Pyati J, Zhu JY, Joy KC, Wilson SJ, Galindo JE, Glass CA, Luo L et al (1999) The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit. J Biol Chem 274: 30799–30810

    PubMed  CAS  Google Scholar 

  25. Hanna MC, Davies PA, Hales TG, Kirkness EF (2000) Evidence for expression of heteromeric serotonin 5-HT(3) receptors in rodents. J Neurochem 75: 240–247

    PubMed  CAS  Google Scholar 

  26. van Hooft JA, Spier AD, Yakel JL, Lummis SC, Vijverberg HP (1998) Promiscuous coassembly of serotonin 5-HT3 and nicotinic alpha4 receptor subunits into Ca(2+)-permeable ion channels. Proc Natl Acad Sci USA 95: 11456–11461

    PubMed  Google Scholar 

  27. Kriegler S, Sudweeks S, Yakel JL (1999) The nicotinic alpha4 receptor subunit contributes to the lining of the ion channel pore when expressed with the 5-HT3 receptor subunit. J Biol Chem 274: 3934–3936

    PubMed  CAS  Google Scholar 

  28. Parker RM, Bentley KR, Barnes NM (1996) Allosteric modulation of 5-HT3 receptors: Focus on alcohols and anaesthetic agents. Trends Pharmacol Sci 17: 95–99

    PubMed  CAS  Google Scholar 

  29. Boess FG, Martin IL (1994) Molecular biology of 5-HT receptors. Neuropharmacology 33: 275–317

    PubMed  CAS  Google Scholar 

  30. Yakel JL, Shao XM, Jackson MB (1991) Activation and desensitization of the 5-HT3 receptor in a rat glioma x mouse neuroblastoma hybrid cell. J Physiol 436: 293–308

    PubMed  CAS  Google Scholar 

  31. Yakel JL, Jackson MB (1988) 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. Neuron 1: 615–621

    PubMed  CAS  Google Scholar 

  32. Waeber C, Hoyer D, Palacios JM (1989) 5-hydroxytryptamine3 receptors in the human brain: Autoradiographic visualization using [3H]ICS 205-930. Neuroscience 31: 393–400

    PubMed  CAS  Google Scholar 

  33. Fozard JR (1984) Neuronal 5-HT receptors in the periphery. Neuropharmacology 23: 1473–1486

    PubMed  CAS  Google Scholar 

  34. Peters JA, Malone HM, Lambert JJ (1991) Ketamine potentiates 5-HT3 receptor-mediated currents in rabbit nodose ganglion neurones. Br J Pharmacol 103: 1623–1625

    PubMed  CAS  Google Scholar 

  35. Wallis DI, Elliott P (1991) The electrophysiology of 5-HT. In: JR Fozard, PR Saxena (eds): Serotonin: Molecular biology, receptors and functional effects. Birkhäuser Verlag, Basel, 203–219

    Google Scholar 

  36. Pratt GD, Bowery NG, Kilpatrick GJ, Leslie RA, Barnes NM, Naylor RJ, Jones BJ, Nelson DR, Palacids JM, Slater P et al (1990) Consensus meeting agrees distribution of 5-HT3 receptors in mammalian hindbrain. Trends Pharmacol Sci 11: 135–137

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  38. Kilpatrick GJ, Jones BJ, Tyers MB (1987) Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature 330: 746–748

    PubMed  CAS  Google Scholar 

  39. Waeber C, Dixon K, Hoyer D, Palacios JM (1988) Localisation by autoradiography of neuronal 5-HT3 receptors in the mouse CNS. Eur J Pharmacol 151: 351–352

    PubMed  CAS  Google Scholar 

  40. Laporte AM, Koscielniak T, Ponchant M, Verge D, Hamon M, Gozlan H (1992) Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodo-zacopride and [3H]zacopride as radioligands. Synapse 10: 271–281

    PubMed  CAS  Google Scholar 

  41. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994) International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46: 157–203

    PubMed  CAS  Google Scholar 

  42. Sugita S, Shen KZ, North RA (1992) 5-hydroxytryptamine is a fast excitatory transmitter at 5-HT3 receptors in rat amygdala. Neuron 8: 199–203

    PubMed  CAS  Google Scholar 

  43. Roerig B, Nelson DA, Katz LC (1997) Fast synaptic signaling by nicotinic acetylcholine and serotonin 5-HT3 receptors in developing visual cortex. J Neurosci 17: 8353–8362

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  45. Bloom FE, Morales M (1998) The central 5-HT3 receptor in CNS disorders. Neurochem Res 23: 653–659

    PubMed  CAS  Google Scholar 

  46. Rondé P, Nichols RA (1997) 5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG108-15 cells via calcium-induced calcium release. Cell Calcium 22: 357–365

    PubMed  Google Scholar 

  47. Rondé P, Nichols RA (1998) High calcium permeability of serotonin 5-HT3 receptors on presynaptic nerve terminals from rat striatum. J Neurochem 70: 1094–1103

    PubMed  Google Scholar 

  48. MacDermott AB, Role LW, Siegelbaum SA (1999) Presynaptic ionotropic receptors and the control of transmitter release. Annu Rev Neurosci 22: 443–485

    PubMed  CAS  Google Scholar 

  49. van Hooft JA, Vijverberg HP (2000) 5-HT(3) receptors and neurotransmitter release in the CNS: A nerve ending story? Trends Neurosci 23: 605–610

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  51. Nichols RA, Mollard P (1996) Direct observation of serotonin 5-HT3 receptor-induced increases in calcium levels in individual brain nerve terminals. J Neurochem 67: 581–592

    PubMed  CAS  Google Scholar 

  52. Nayak SV, Ronde P, Spier AD, Lummis SC, Nichols RA (1999) Calcium changes induced by presynaptic 5-hydroxytryptamine-3 serotonin receptors on isolated terminals from various regions of the rat brain. Neuroscience 91: 107–117

    PubMed  CAS  Google Scholar 

  53. Feuerstein TJ, Hertting G (1986) Serotonin (5-HT) enhances hippocampal noradrenaline (NA) release: evidence for facilitatory 5-HT receptors within the CNS. Naunyn Schmiedebergs Arch Pharmacol 333: 191–197

    PubMed  CAS  Google Scholar 

  54. Parsons LH, Justice JB Jr (1993) Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. Brain Res 606: 195–199

    PubMed  CAS  Google Scholar 

  55. De Deurwaerdere P, Stinus L, Spampinato U (1998) Opposite change of in vivo dopamine release in the rat nucleus accumbens and striatum that follows electrical stimulation of dorsal raphe nucleus: Role of 5-HT3 receptors. J Neurosci 18: 6528–6538

    PubMed  Google Scholar 

  56. Kawamata T, Omote K, Toriyabe M, Yamamoto H, Namiki A (2003) The activation of 5-HT(3) receptors evokes GABA release in the spinal cord. Brain Res 978: 250–255

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  58. Barnes JM, Barnes NM, Costall B, Naylor RJ, Tyers MB (1989) 5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue. Nature 338: 762–763

    PubMed  CAS  Google Scholar 

  59. Maura G, Andrioli GC, Cavazzani P, Raiteri M (1992) 5-Hydroxytryptamine3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release. J Neurochem 58: 2334–2337

    PubMed  CAS  Google Scholar 

  60. Blier P, Bouchard C (1993) Functional characterization of a 5-HT3 receptor which modulates the release of 5-HT in the guinea-pig brain. Br J Pharmacol 108: 13–22

    PubMed  CAS  Google Scholar 

  61. Bagdy E, Solyom S, Harsing LG Jr (1998) Feedback stimulation of somatodendritic serotonin release: A 5-HT3 receptor-mediated effect in the raphe nuclei of the rat. Brain Res Bull 45: 203–208

    PubMed  CAS  Google Scholar 

  62. Funahashi M, Mitoh Y, Matsuo R (2004) Activation of presynaptic 5-HT3 receptors facilitates glutamatergic synaptic inputs to area postrema neurons in rat brain slices. Methods Find Exp Clin Pharmacol 26: 615–622

    PubMed  CAS  Google Scholar 

  63. Richardson BP, Engel G, Donatsch P, Stadler PA (1985) Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316: 126–131

    PubMed  CAS  Google Scholar 

  64. Kilpatrick GJ, Butler A, Burridge J, Oxford AW (1990) 1-(m-Chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist. Eur J Pharmacol 182: 193–197

    PubMed  CAS  Google Scholar 

  65. Dukat M, Abdel-Rahman AA, Ismaiel AM, Ingher S, Teitler M, Gyermek L, Glennon RA (1996) Structure-activity relationships for the binding of arylpiperazines and arylbiguanides at 5-HT3 serotonin receptors. J Med Chem 39: 4017–4026

    PubMed  CAS  Google Scholar 

  66. Bockaert J, Fozard JR, Dumuis A, Clarke DE (1992) The 5-HT4 receptor: A place in the sun. Trends Pharmacol Sci 13: 141–145

    PubMed  CAS  Google Scholar 

  67. Saxena PR, Villalon CM (1991) 5-Hydroxytryptamine: A chameleon in the heart. Trends Pharmacol Sci 12: 223–227

    PubMed  Google Scholar 

  68. Blauw GJ, van Brummelen P, Chang PC, Vermeij P, van Zwieten PA (1988) 5HT3 receptor-mediated vasodilation in the human forearm. J Hypertens Suppl 6: S33–S35

    PubMed  CAS  Google Scholar 

  69. McQueen DS, Mir A (1989) 5-Hydroxytryptamine and cardiopulmonary and carotid body reflex mechanisms. In: JR Fozard (ed): The peripheral actions of 5-hydroxytryptamine. Oxford University Press, Oxford, 301–326

    Google Scholar 

  70. De Ponti F, Tonini M (2001) Irritable bowel syndrome: New agents targeting serotonin receptor subtypes. Drugs 61: 317–332

    PubMed  Google Scholar 

  71. Loisy C, Beorchia S, Beorchia S, Centonze V, Fozard JR, Schechter PJ, Tell GP (1985) Effects on migraine headache of MDL 72,222, an antagonist at neuronal 5-HT receptors. Double-blind, placebo-controlled study. Cephalagia 5: 79–82

    CAS  Google Scholar 

  72. Gralla R (1995) The clinical approach to chemotherapy-induced emesis. In: DJM Reynolds, PLR Andrews, CJ Davis (eds): Serotonin and the scientific basis of antiemetic therapy. Oxford Clinical Communications, Oxford, 111–126

    Google Scholar 

  73. Marty M (1993) Future trends in cancer treatment and emesis control. Oncology 50: 159–162

    PubMed  CAS  Google Scholar 

  74. Costall B, Kelly ME, Naylor RJ, Onaivi ES, Tyers MB (1989) Neuroanatomical sites of action of 5-HT3 receptor agonist and antagonists for alteration of aversive behaviour in the mouse. Br J Pharmacol 96: 325–332

    PubMed  CAS  Google Scholar 

  75. Barnes JM, Barnes NM, Cooper SJ (1992) Behavioural pharmacology of 5-HT3 receptor ligands. Neurosci Biobehav Rev 16: 107–113

    PubMed  CAS  Google Scholar 

  76. Costall B, Naylor RJ (1994) 5-HT3 receptor antagonists in the treatment of cognitive disorders. In: FD King, FD Jones, BJ Sanger, GJ Boca Raton (eds): 5-Hydroxytryptamine-3 receptor antagonists in the treatment of cognitive disorders. CRC Press, Boca Raton, 203–220

    Google Scholar 

  77. Iversen SD (1984) 5-HT and anxiety. Neuropharmacology 23: 1553–1560

    PubMed  CAS  Google Scholar 

  78. Johnston AL, File SE (1986) 5-HT and anxiety: promises and pitfalls. Pharmacol Biochem Behav 24: 1467–1470

    PubMed  CAS  Google Scholar 

  79. Kelly SP, Bratt AM, Hodge CW (2003) Targeted gene deletion of the 5-HT3A receptor subunit produces an anxiolytic phenotype in mice. Eur J Pharmacol 461: 19–25

    Google Scholar 

  80. Eisensamer B, Rammes G, Gimpl G, Shapa M, Ferrari U, Hapfelmeier G, Bondy B, Parsons C, Gilling K, Zieglgansberger W et al (2003) Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor. Mol Psychiatry 8: 994–1007

    PubMed  CAS  Google Scholar 

  81. Hui SC, Sevilla EL, Ogle CW (1993) 5-HT3 antagonists reduce morphine self-administration in rats. Br J Pharmacol 110: 1341–1346

    PubMed  CAS  Google Scholar 

  82. Kostowski W, Dyr W, Krzascik P (1993) The abilities of 5-HT3 receptor antagonist ICS 205-930 to inhibit alcohol preference and withdrawal seizures in rats. Alcohol 10: 369–373

    PubMed  CAS  Google Scholar 

  83. Doty P, Zacny JP, de Wit H (1994) Effects of ondansetron pretreatment on acute responses to ethanol in social drinkers. Behav Pharmacol 5: 461–469

    PubMed  CAS  Google Scholar 

  84. Warburton EC, Joseph MH, Feldon J, Weiner I, Gray JA (1994) Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: Implications for a possible antipsychotic action of ondansetron. Psychopharmacology (Berl) 114: 657–664

    CAS  Google Scholar 

  85. Sirota P, Mosheva T, Shabtay H, Giladi N, Korczyn AD (2000) Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia. Am J Psychiatry 157: 287–289

    PubMed  CAS  Google Scholar 

  86. Tissier MH, Franc B, Hamon M, Adrien J (1990) Effect of 5-HT1A and 5-HT3-receptor ligands on sleep in the rat. In: J Horne (ed): Sleep 90. Pontenagel Press, Bochum, 126–128

    Google Scholar 

  87. Monti JM, Monti D (2000) Role of dorsal raphe nucleus serotonin 5-HT1A receptor in the regulation of REM sleep. Life Sci 66: 1999–2012

    PubMed  CAS  Google Scholar 

  88. Van Bockstaele EJ, Biswas A, Pickel VM (1993) Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens. Brain Res 624: 188–198

    PubMed  Google Scholar 

  89. Hagan RM, Butler A, Hill JM, Jordan CC, Ireland SJ, Tyers MB (1987) Effect of the 5-HT3 receptor antagonist, GR38032F, on responses to injection of a neurokinin agonist into the ventral tegmental area of the rat brain. Eur J Pharmacol 138: 303–305

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  91. Monti JM, Jantos H, Fernandez M (1989) Effects of the selective dopamine D-2 receptor agonist, quinpirole on sleep and wakefulness in the rat. Eur J Pharmacol 169: 61–66

    PubMed  CAS  Google Scholar 

  92. Van Bockstaele EJ, Pickel VM (1993) Ultrastructure of serotonin-immunoreactive terminals in the core and shell of the rat nucleus accumbens: cellular substrates for interactions with catecholamine afferents. J Comp Neurol 334: 603–617

    PubMed  Google Scholar 

  93. Monti JM, Ponzoni A, Jantos H, Lagos P, Silveira R, Banchero P (1999) Effects of accumbens m-chlorophenylbiguanide microinjections on sleep and waking in intact and 6-hydroxydopamine-treated rats. Eur J Pharmacol 364: 89–98

    PubMed  CAS  Google Scholar 

  94. Graff C, Challet E, Pevet P, Wollnik F (2007) 5-HT3 receptor-mediated photic-like responses of the circadian clock in the rat. Neuropharmacology 52: 662–671

    PubMed  CAS  Google Scholar 

  95. Morin LP (1994) The circadian visual system. Brain Res Rev 19: 102–127

    PubMed  CAS  Google Scholar 

  96. Graff C, Kohler M, Pevet P, Wollnik F (2005) Involvement of the retinohypothalamic tract in the photic-like effects of the 5-HT agonist quipazine in the rat. Neuroscience 135: 273–283

    PubMed  CAS  Google Scholar 

  97. Prosser RA, Dean RR, Edgar DM, Heller HC, Miller JD (1993) Serotonin and the mammalian circadian system: I. In vitro phase shifts by serotonergic agonists and antagonists. J Biol Rhythms 8: 1–16

    PubMed  CAS  Google Scholar 

  98. Roca AL, Weaver DR, Reppert SM (1993) Serotonin receptor gene expression in the rat suprachiasmatic nuclei. Brain Res 608: 159–165

    PubMed  CAS  Google Scholar 

  99. Young T, Palta M, Dempsey J Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328: 1230–1235

    PubMed  CAS  Google Scholar 

  100. Day R, Gerhardstein R, Lumley A, Roth T, Rosenthal L (1999) The behavioral morbidity of obstructive sleep apnea. Prog Cardiovasc Dis 41: 341–354

    PubMed  CAS  Google Scholar 

  101. Peker Y, Hedner J, Kraiczi H, Loth S (2000) Respiratory disturbance index: An independent predictor of mortality in coronary artery disease. Am J Respir Crit Care Med 162: 81–86

    PubMed  CAS  Google Scholar 

  102. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, O’Connor GT, Boland LL, Schwartz JE, Samet JM (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163: 19–25

    PubMed  CAS  Google Scholar 

  103. Strohl KP, Hensley MJ, Hallett M Saunders NA, Ingram RH Jr (1980) Activation of upper airway muscles before onset of inspiration in normal humans. J Appl Physiol 49: 638–642

    PubMed  CAS  Google Scholar 

  104. Goh AS, Issa FG, Sullivan CE (1986) Upper airway dilating forces during wakefulness and sleep in dogs. J Appl Physiol 61: 2148–2155

    PubMed  CAS  Google Scholar 

  105. Parisi RA, Neubauer JA, Frank MM, Edelman NH, Santiago TV (1987) Correlation between genioglossal and diaphragmatic responses to hypercapnia during sleep. Am Rev Respir Dis 135: 378–382

    PubMed  CAS  Google Scholar 

  106. Mezzanotte WS, Tangel DJ, White DP (1996) Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am J Respir Crit Care Med 153: 1880–1887

    PubMed  CAS  Google Scholar 

  107. Ribeiro-do-Valle LE, Metzler CW, Jacobs BL (1991) Facilitation of masseter EMG and masseteric (jaw-closure) reflex by serotonin in behaving cats. Brain Res 550: 197–204

    PubMed  CAS  Google Scholar 

  108. Kubin L, Tojima H, Davies RO, Pack AI (1992) Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat. Neurosci Lett 139: 243–248

    PubMed  CAS  Google Scholar 

  109. Douse MA, White DP (1996) Serotonergic effects on hypoglossal neural activity and reflex responses. Brain Res 726: 213–222

    PubMed  CAS  Google Scholar 

  110. Heym J, Steinfels GF, Jacobs JB (1982) Activity of serotonin-containing neurons in the nucleus raphe pallidus of freely moving cats. Brain Res 16: 259–276

    Google Scholar 

  111. Jelev A, Sood S, Liu H, Nolan P, Horner RL (2001) Microdialysis perfusion of 5-HT into hypoglossal motor nucleus differentially modulates genioglossus activity across natural sleep-wake states in rats. J Physiol 532: 467–481

    PubMed  CAS  Google Scholar 

  112. Kubin L, Reignier C, Tojima H, Taguchi O, Pack AI, Davies RO (1994) Changes in serotonin level in the hypoglossal nucleus region during carbachol-induced atonia. Brain Res 645: 291–302

    PubMed  CAS  Google Scholar 

  113. Fenik B, Davies RO, Kubin L (2005) REM sleep-like atonia of hypoglossal (XII) motoneurons is caused by loss of noradrenergic and serotonergic inputs. Am J Respir Crit Care Med 172: 1322–1330

    PubMed  Google Scholar 

  114. Veasey SC, Panckeri KA, Hoffman EA Pack AI, Hendricks JC (1996) The effects of serotonin antagonists in an animal model of sleep-disordered breathing. Am J Respir Crit Care Med 153: 776–786

    PubMed  CAS  Google Scholar 

  115. Veasey SC, Fenik P, Panckeri K, Pack AI, Hendricks JC (1999) The effects of trazodone with l-tryptophan on sleep-disordered breathing in the English bulldog. Am J Respir Crit Care Med 160: 1659–1667

    PubMed  CAS  Google Scholar 

  116. Fenik P, Veasey SC (2003) Pharmacological characterization of serotonergic receptor activity in the hypoglossal nucleus. Am J Respir Crit Care Med 167: 563–569

    PubMed  Google Scholar 

  117. Brandes IF, Zuperku EJ, Dean C, Hopp FA, Jakovcevic D, Stuth EA (2007) Retrograde labeling reveals extensive distribution of genioglossal motoneurons possessing 5-HT2A receptors throughout the hypoglossal nucleus of adult dogs. Brain Res 1132: 110–119

    PubMed  CAS  Google Scholar 

  118. Fenik P, Ogawa H, Veasey SC (2001) Hypoglossal nerve response to 5-HT3 drugs injected into the XII nucleus and vena cava in the rat. Sleep 24: 871–878

    PubMed  CAS  Google Scholar 

  119. Zhan G, Shaheen F, Mackiewicz M, Fenik P, Veasey SC (2002) Single cell laser dissection with molecular beacon polymerase chain reaction identifies 2A as the predominant serotonin receptor subtype in hypoglossal motoneurons. Neuroscience 113: 145–154

    PubMed  CAS  Google Scholar 

  120. Carley DW, Radulovacki M (1999) Role of peripheral serotonin in the regulation of central sleep apneas in rats. Chest 115: 1397–1401

    PubMed  CAS  Google Scholar 

  121. Vardhan A, Kachroo A, Sapru HN (1993) Excitatory amino acid receptors in the nucleus tractus solitarius mediate the responses to the stimulation of cardio-pulmonary vagal afferent C fiber endings. Brain Res 618: 23–31

    PubMed  CAS  Google Scholar 

  122. Sutton PM (1981) The interaction between reflex apnoea and bradycardia produced by injecting 5-HT into the nodose ganglion of the cat. Pflugers Arch 389: 181–187

    PubMed  CAS  Google Scholar 

  123. Yoshioka M, Goda Y, Togashi H, Matsumoto M, Saito H (1992) Pharmacological characterization of 5-hydroxytryptamine-induced apnea in the rat. J Pharmacol Exp Ther 260: 917–924

    PubMed  CAS  Google Scholar 

  124. Radulovacki M, Trbovic SM, Carley DW (1998) Serotonin 5-HT3-receptor antagonist GR 38032F suppresses sleep apneas in rats. Sleep 21: 131–136

    PubMed  CAS  Google Scholar 

  125. Veasey SC, Chachkes J, Fenik P, Hendricks JC (2001) The effects of ondansetron on sleep-disordered breathing in the English bulldog. Sleep 24: 155–160

    PubMed  CAS  Google Scholar 

  126. Schmidt HS (1983) L-tryptophan in the treatment of impaired respiration in sleep. Bull Eur Physiopathol Respir 19: 625–629

    PubMed  CAS  Google Scholar 

  127. Mendelson WB, Martin JV, Rapoport DM (1990) Effects of buspirone on sleep and respiration. Am Rev Respir Dis 141: 1527–1530

    PubMed  CAS  Google Scholar 

  128. Hanzel DA, Proia NG, Hudgel DW (1991) Response of obstructive sleep apnea to fluoxetine and protriptyline. Chest 100: 416–421

    PubMed  CAS  Google Scholar 

  129. Kraiczi H, Hedner J, Dahlof P Ejnell H, Carlson J (1999) Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea. Sleep 22: 61–67

    PubMed  CAS  Google Scholar 

  130. Stradling J, Smith D, Radulovacki M, Carley D (2003) Effect of ondansetron on moderate obstructive sleep apnoea, a single night, placebo-controlled trial. J Sleep Res 12: 169–170

    PubMed  Google Scholar 

  131. Carley DW, Olopade C, Ruigt GS, Radulovacki M (2007) Efficacy of mirtazapine in obstructive sleep apnea syndrome. Sleep 30: 35–41

    PubMed  Google Scholar 

  132. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P et al (1990) The American College of Rheumatology. Criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 33: 160–172

    PubMed  CAS  Google Scholar 

  133. Goldenberg DL (1999) Fibromyalgia syndrome a decade later: what have we learned? Arch Intern Med 159: 777–785

    PubMed  CAS  Google Scholar 

  134. McCain GA (1996) A cost-effective approach to the diagnosis and treatment of fibromyalgia. Rheum Dis Clin North Am 22: 323–349

    PubMed  CAS  Google Scholar 

  135. Arnold LM (2006) Biology and therapy of fibromyalgia. New therapies in fibromyalgia. Arthritis Res Ther 8: 212

    Google Scholar 

  136. Moldofsky H, McFarlane JG (2005) Fibromyalgia and chronic fatigue syndromes. In: MH Kryger, T Roth, WC Dement (eds): Principles and practice of sleep medicine, 4th edn. Elsevier Saunders, Philadelphia, 1125–1236

    Google Scholar 

  137. Rang HP, Bevan S, Dray A (1994) Nociceptive peripheral neurons: Cellular properties. In: PD Wall, R Melzack (eds): The textbook of pain. Churchill Livingstone, London, 57–78

    Google Scholar 

  138. Giordano J, Rogers LV (1989) Peripherally administered serotonin 5-HT3 receptor antagonists reduce inflammatory pain in rats. Eur J Pharmacol 170: 83–86

    PubMed  CAS  Google Scholar 

  139. Sufka KJ, Schomburg FM, Giordano J (1992) Receptor mediation of 5-HT-induced inflammation and nociception in rats. Pharmacol Biochem Behav 41: 53–56

    PubMed  CAS  Google Scholar 

  140. Zeitz KP, Guy N, Malmberg AB Dirajlal S, Martin WJ, Sun L, Bonhaus DW, Stucky CL, Julius D, Basbaum AI (2002) The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci 22: 1010–1019

    PubMed  CAS  Google Scholar 

  141. Färber L, Stratz T, Brückle W, Spath M, Pongratz D, Lautenschlager J, Kotter I, Zoller B, Peter HH, Neeck G et al (2001) Short-term treatment of primary fibromyalgia with the 5-HT3 antagonist tropisetron. Results of a randomized, double-blind placebo controlled multicentre trial in 418 patients. Int J Clin Pharmacol Res 21: 1–13

    PubMed  Google Scholar 

  142. Papadopoulos IA, Georgiou PE, Katsimbri PP, Drosos AA (2000) Treatment of fibromyalgia with tropisetron, a 5HT3 serotonin antagonist: A pilot study. Clin Rheumatol 19: 6–8

    PubMed  CAS  Google Scholar 

  143. Müller W, Stratz T (2001) Results of intravenous administration of tropisetron in fibromylagia patients. Scand J Rheumatol Suppl 113: 59–62

    Google Scholar 

  144. Köppe C, Schneider C, Thieme K, Mense S, Stratz T, Muller W, Flor H (2004) The influence of the 5-HT3 receptor antagonist tropisetron on pain in fibromyalgia: A functional magnetic resonance imaging pilot study. Scand J Rheumatol Suppl 119: 24–27

    Google Scholar 

  145. Samborski W, Lezanska-Szpera M, Rybakowski JK (2004) Effects of antidepressant mirtazapine on fibromyalgia symptoms. Rocz Akad Med Bialymst 49: 265–269

    PubMed  CAS  Google Scholar 

  146. Kohnen R, Färber L, Spath M (2004) The assessment of vegetative and functional symptoms in fibromyalgia patients: The tropisetron experience. Scand J Rheumatol Suppl 119: 67–71

    PubMed  Google Scholar 

  147. Saria A, Javorsky F, Humpel C, Gamse R (1990) 5-HT3 receptors antagonists inhibit sensory neuropeptides release from the rat spinal cord. Neuroreport 1: 104–106

    PubMed  CAS  Google Scholar 

  148. Moore KA, Oh EJ, Weinreich D (2002) 5-HT3 receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro. J Appl Physiol 92: 2529–2534

    PubMed  CAS  Google Scholar 

  149. Stratz T, Fiebich B, Haus U, Mueller W (2004) Influence of tropisetron on the serum substance P levels in fibromyalgia patients. Scand J Rheumatol 33: 41–43

    Google Scholar 

  150. Schwarz MJ, Spath M, Muller-Bardorff H, Pongratz DE, Bondy B, Ackenheil M (1999) Relationship of substance P, 5-hydroxyindole acetic acid and tryptophan in serum of fibromyalgia patients. Neurosci Lett 259: 196–198

    PubMed  CAS  Google Scholar 

  151. Andersen ML, Nascimento DC, Machado RB, Roizenblatt S, Moldofsky H, Tufik S (2006) Sleep disturbance induced by substance P in mice. Behav Brain Res 167: 212–218

    PubMed  CAS  Google Scholar 

  152. Lieb K, Ahlvers K, Dancker K, Strohbusch S, Reincke M, Feige B, Berger M, Riemann D, Voderholzer U (2002) Effects of the neuropeptide substance P on sleep, mood, and neuroendocrine measures in healthy young men. Neuropsychopharmacology 27: 1041–1049

    PubMed  CAS  Google Scholar 

  153. Field T, Diego M, Cullen C, Hernandez-Reif M, Sunshine W, Douglas S (2002) Fibromyalgia pain and substance P decrease and sleep improves after massage therapy. J Clin Rheumatol 8: 72–76

    PubMed  Google Scholar 

  154. Idzikowski C, Mills FJ, Glennard R (1986) 5-Hydroxytryptamine-2 antagonist increases human slow wave sleep. Brain Res 378: 164–168

    PubMed  CAS  Google Scholar 

  155. Staner L, Kempenaers C, Simonnet MP, Fransolet L, Mendlewicz J (1992) 5-HT2 receptor antagonism and slow-wave sleep in major depression. Acta Psychiatr Scand 86: 133–137

    PubMed  CAS  Google Scholar 

  156. Sharpley AL, Elliott JM, Attenburrow MJ, Cowen PJ (1994) Slow wave sleep in humans: Role of 5-HT2A and 5-HT2C receptors. Neuropharmacology 33: 467–471

    PubMed  CAS  Google Scholar 

  157. Boutrel B, Franc B, Hen R, Hamon M, Adrien J (1999) Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knockout mice. J Neurosci 19: 3204–3212

    PubMed  CAS  Google Scholar 

  158. Boutrel B, Monaca C, Hen R Hamon M, Adrien J (2002) Involvement of 5-HT1A receptors in homeostatic and stress-induced adaptive regulations of paradoxical sleep: studies in 5-HT1A knockout mice. J Neurosci 22: 4686–4692

    PubMed  CAS  Google Scholar 

  159. Thompson AJ, Lummis SC (2003) A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor. Br J Pharmacol 140: 359–365

    PubMed  CAS  Google Scholar 

  160. Hope AG, Peters JA, Brown AM, Lambert JJ, Blackburn TP (1996) Characterization of a human 5-hydroxytryptamine3 receptor type A (h5-HT3R-AS) subunit stably expressed in HEK 293 cells. Br J Pharmacol 118: 1237–1245

    PubMed  CAS  Google Scholar 

  161. Steward LJ, Ge J, Bentley KR, Barber PC, Hope AG, Lambert JJ, Peters JA, Blackburn TP, Barnes NM (1995) Evidence that the atypical 5-HT3 receptor ligand, [3H]-BRL46470, labels additional 5-HT3 binding sites compared to [3H]-granisetron. Br J Pharmacol 116: 1781–1788

    PubMed  CAS  Google Scholar 

  162. Dubin AE, Huvar R, D’Andrea MR, Pyati J, Zhu JY, Joy KC, Wilson SJ, Galindo JE, Glass CA, Luo L, et al. (1999) The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit. J Biol Chem 274: 30799–30810

    PubMed  CAS  Google Scholar 

  163. Downie DL, Hope AG, Lambert JJ, Peters JA, Blackburn TP, Jones BJ (1994) Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes. Neuropharmacology 33: 473–482

    PubMed  CAS  Google Scholar 

  164. Bachy A, Héaulme M, Giudice A, Michaud JC, Lefevre IA, Souilhac J, Manara L, Emerit MB, Gozlan H, Hamon M, et al. (1993) SR 57227A: a potent and selective agonist at central and peripheral 5-HT3 receptors in vitro and in vivo. Eur J Pharmacol. 237: 299–309

    PubMed  CAS  Google Scholar 

  165. Peters JA, Malone HM, Lambert JJ (1993) An electrophysiological investigation of the properties of 5-HT3 receptors of rabbit nodose ganglion neurones in culture. Br J Pharmacol 110: 665–676

    PubMed  CAS  Google Scholar 

  166. Gill CH, Peters JA, Lambert JJ (1995) An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells. Br J Pharmacol 114: 1211–1221

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Forenap — Institute for Research in Neurosciences, Neuropharmacology and Psychiatry, Centre Hospitalier, 27 rue du 4eme R.S.M., 68250, Rouffach, France

    Luc Staner, Caroline Graff, Remy Luthrhinger & Nadine Noel

Authors
  1. Luc Staner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caroline Graff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Remy Luthrhinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nadine Noel
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montevideo, 11300, Uruguay

    Jaime M. Monti

  2. Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street - Rm # BB813, New York, NY, 10032, USA

    S. R. Pandi-Perumal

  3. Green Hall, Program in Neuroscience, Princeton University, Princeton, NJ, 08540, USA

    Barry L. Jacobs

  4. Psychopharmacology Unit, Dorothy Hodgkin Building Whitson Street, Bristol, BS1 3NY, UK

    David J. Nutt

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Staner, L., Graff, C., Luthrhinger, R., Noel, N. (2008). Effect of the selective activation of serotonin 5-HT3 receptors on sleep and waking. In: Monti, J.M., Pandi-Perumal, S.R., Jacobs, B.L., Nutt, D.J. (eds) Serotonin and Sleep: Molecular, Functional and Clinical Aspects. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8561-3_16

Download citation

Publish with us

Policies and ethics

Search

Navigation