The role of 5-hydroxytryptamine in the regulation of sympathetic nerve discharge

  • Robert B. McCall
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)


A large amount of evidence has accumulated to indicate that central serotonergic (5-hydroxytryptamine, 5-HT) neurons participate in the regulation of sympathetic nerve discharge (SND) and, therefore, blood pressure. Areas of the brain stem and spinal cord involved in vasomotor control are heavily innervated by 5-HT neurons [1, 2]. The area of the midline medulla that contains 5-HT neurons which project to autonomic nuclei corresponds to the classic medullary depressor region [3]. The close association between 5-HT descending neurons and midline sites that elicit vasodepressor responses when electrically stimulated has led to the conclusion that descending 5-HT medullospinal pathways inhibit sympathetic preganglionic neurons [4–7]. The findings that stimulation of presumed 5-HT-containing axons in the dorsolateral funiculus of the spinal cord inhibits sympathetic activity supports this hypothesis [8]. Early pharmacological studies based on the effects of 5-HT precursors and synthesis inhibitors support the concept that 5-HT neurons normally inhibit transmission in central sympathetic pathways. For example, administration of the 5-HT precursor 5-hydroxytryptophan results in a decrease in mean arterial blood pressure (MAP), heart rate (HR) and SND [9]. Furthermore, precursor administration produces a dose-dependent depression of spinal sympathetic reflexes. Taken together, these data suggest that central 5-HT neurons inhibit sympathetic neurons. However, a great deal of data generated in our laboratory suggests that 5-HT neurons excite rather than inhibit sympathetic neurons in the central nervous system. This chapter is intended to review this data with particular emphasis paid to the type of 5-HT receptor subtypes involved in the regulation of sympathetic neurons.


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  1. 1.
    Fuxe K (1965): Evidence for the existence of monoamine neurons in the CNS. IV. The distribution of monoamine terminals in the CNS. Acta Physiol Scand 64 (suppl. 247): 38 – 85.Google Scholar
  2. 2.
    Bobillier P, Sequin S, Petitjean F, Salvert D, Touret M, Jouvet M (1976): The raphe nuclei of the cat brain stem: A topographical atlas of their efferent projections as revealed by autoradiography. Brain Res 113: 449 – 486.PubMedCrossRefGoogle Scholar
  3. 3.
    Wang SC, Ranson SW (1939): Autonomic responses to electrical stimulation of the lower brain stem. J Comp Neurol 71: 437 – 455.CrossRefGoogle Scholar
  4. 4.
    Cabot JB, Wild J, Cohen DN (1979): Raphe inhibition of sympathetic preganglionic neurons. Science 203: 184 – 186.PubMedCrossRefGoogle Scholar
  5. 5.
    Coote JH, Macleod VH (1974): The influence of bulbospinal monoaminergic pathways on sympathetic nerve activity. J Physiol (London) 241: 453 – 475.Google Scholar
  6. 6.
    Gilbey MP, Coote JH, Macleod VH, Peterson DF (1981): Inhibition of sympathetic activity by stimulating in the raphe nuclei and the role of 5-hydroxytryptamine in this effect. Brain Res 226: 131 – 142.PubMedCrossRefGoogle Scholar
  7. 7.
    Howe PRC (1985): Blood pressure control by neurotransmitters in the medulla oblongata and spinal cord. J Auton Nerv Syst 12: 95 – 115.PubMedCrossRefGoogle Scholar
  8. 8.
    Coote JH, Macleod VH (1975): The spinal route of sympathoinhibitory pathways descending from the medulla. Pflugers Arch 359: 335 – 347.PubMedCrossRefGoogle Scholar
  9. 9.
    Kuhn DM, Wolf WA, Lovenberg W (1980): Review of the role of the central serotonergic neuronal system in blood pressure. Hypertension 2: 243 – 255.PubMedCrossRefGoogle Scholar
  10. 10.
    McCall RB, Humphrey SJ (1982): Involvement of serotonin in the central regulation of blood pressure: evidence for a facilitation effect on sympathetic nerve activity. J Pharmacol exp Therap 222: 94 – 102.Google Scholar
  11. 11.
    McCall RB, Harris LT (1987): Sympathetic alterations after midline medullary raphe lesions. Am J Physiol 253: R91 – R107.Google Scholar
  12. 12.
    Aghajanian GK, Wang RY (1978): Physiology and pharmacology of central serotonergic neurons, pp. 171–183 in: Lipton MA, DiMascio A, Killam KF (eds), Psychopharmacology: A Generation of Progress. New York: Raven Press.Google Scholar
  13. 13.
    Loewy AD (1981): Raphe pallidus and raphe obscurus projections to the intermediolateral cell column in the rat. Brain Res 222: 129 – 133.PubMedCrossRefGoogle Scholar
  14. 14.
    Loewy AD, McKellar S (1981): Serotonergic projections from the ventral medulla to the intermediolateral cell column in the rat. Brain Res 211: 146 – 152.PubMedCrossRefGoogle Scholar
  15. 15.
    McCall RB (1983): Serotonergic excitation of sympathetic preganglionic neurons: a microiontophoretic study. Brain Res 289: 121 – 127.PubMedCrossRefGoogle Scholar
  16. 16.
    McCall RB (1984): Evidence for a serotonergically mediated sympathoexcitatory response to stimulation of medullary raphe nuclei. Brain Res 311: 131 – 139.PubMedCrossRefGoogle Scholar
  17. 17.
    McCall RB, Humphrey SJ (1985): Evidence for GABA mediation of sympathetic inhibition evoked from midline medullary depressor sites. Brain Res 339: 356 – 361.PubMedCrossRefGoogle Scholar
  18. 18.
    McCall RB, Humphrey SJ (1985): Evidence for GABA mediation of sympathetic inhibition evoked from midline medullary depressor sites. Brain Res 339: 356 – 361.PubMedCrossRefGoogle Scholar
  19. 19.
    McCall RB, Patel BN, Harris LT (1987): Effects of serotonin1 and serotonin2 receptor agonists and antagonists on blood pressure, heart rate and sympathetic nerve activity. J Pharmacol exp Therap 242: 1152 – 1159.Google Scholar
  20. 20.
    McCall RB, Schuette MR (1984): Evidence for the alpha-1 receptor-mediated central sympathoinhibitory action of ketanserin./ Pharmacol exp Therap 228: 704 – 710.Google Scholar
  21. 21.
    McCall RB, Humphrey SJ (1981): Evidence for a central depressor action of postsynaptic alpha-1 adrenergic antagonists. J Auton Nerv Syst 3: 9 – 23.PubMedCrossRefGoogle Scholar
  22. 22.
    McCall RB, Harris LT (1987): Characterization of the central sympathoinhibitory action of ketanserin. J Pharmacol exp Therap 241: 736 – 740.Google Scholar
  23. 23.
    Fozard JR, Mir AK, Middlemiss DN (1987): The cardiovascular response to 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis. J Cardiovasc Pharmacol 9: 328 – 347.PubMedCrossRefGoogle Scholar
  24. 24.
    Ramage AG, Fozard JR (1987): Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and isapirone, have a central hypotensive action that differs from that of clonidine in anaesthetized cats. Europ J Pharmacol 138: 179 – 191.CrossRefGoogle Scholar
  25. 25.
    Verge D, Daval G, Patey A, Gozlan H, El Mestikaway S, Hamon M (1985): Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. European J Pharmacol 113: 463 – 464.CrossRefGoogle Scholar
  26. 26.
    Chiang CY, Pan ZZ (1985): Differential responses of serotonergic and non-serotonergic neurons in nucleus raphe magnus to systemic morphine in rats. Brain Research 337: 146 – 150.PubMedCrossRefGoogle Scholar
  27. 27.
    Wei JB, Chiang CC (1986): Responses of serotonergic and non-serotonergic neurons in the rat nucleus raphe magnus to systemic lysergic acid diethylamide. Neuroscience Research 3: 268 – 273.PubMedCrossRefGoogle Scholar
  28. 28.
    Heym J, Steinfels GF, Jacobs BL (1982): Activity of serotonin-containing neurons in the nucleus raphe pallidus of freely moving cats. Brain Research 251: 259 – 276.PubMedCrossRefGoogle Scholar
  29. 29.
    Wessendorf MW, Anderson EG (1983): Single unit studies of identified bulbospinal serotonergic units. Brain Research 279: 93 – 103.PubMedCrossRefGoogle Scholar
  30. 30.
    Heym J, Steinfels GF, Jacobs BL (1982): Medullary serotonergic neurons are insensitive to 5-MeODMT and LSD. European J Pharmacol 81: 677 – 680.CrossRefGoogle Scholar
  31. 31.
    Jacobs BL, Heym J, Rasmussen K (1983): Raphe neurons: firing rate correlates with size of drug response. European J Pharmacol 90: 275 – 278.CrossRefGoogle Scholar
  32. 32.
    Wang RY, Aghajanian GK (1977): Antidromically identified serotonergic neurons in the rat midbrain raphe: evidence for collateral inhibition. Brain Research 132: 186 – 193.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang RY, Aghajanian GK (1982): Correlative firing patterns of serotonergic neurons in rat dorsal raphe nucleus. J Neuroscience 2: 11 – 16.Google Scholar
  34. 34.
    McCall RB, Clement ME (1988): Identification of serotonergic and sympathetic neurons in medullary raphe nuclei. Brain Research 477: 172 – 182.CrossRefGoogle Scholar
  35. 35.
    Morilak DA, Fornal C, Jacobs BL (1986): Single unit activity of noradrenergic neurons in locus coeruleus and serotonergic neurons in the nucleus raphe dorsalis of freely moving cats in relation to the cardiac cycle. Brain Research 399: 262 – 270.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 1990

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  • Robert B. McCall

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