Advertisement

Serotonin pp 95-100 | Cite as

5-HT3 Receptors in the Central Nervous System

  • M. B. Tyers
  • B. Costall
  • R. J. Naylor
Part of the Satellite Symposia of the IUPHAR 10th International Congress of Pharmacology book series (SSNIC)

Abstract

The presence of 5-HT3 receptor-mediated responses in peripheral tissues is well established. Their presence in the CNS is implied by the powerful behavioural effects produced by 5-HT3 receptor antagonists in laboratory animals (Costall et al., 1987a, b; Jones et al., 1987, 1988; Tyers et al., 1987). However, despite the high selectivity of action of these compounds for the 5-HT3 receptor, there is no direct evidence that 5-HT3 receptors are present in the brain. Three series of experiments have been conducted to address this issue: functional studies on central 5-HT pathways; effects on mesolimbic dopamine metabolism; and binding studies with a novel [3H]-labelled 5-HT3 receptor antagonist.

Keywords

Nucleus Accumbens Ventral Tegmental Area Dorsal Raphe Nucleus Anxiolytic Activity Lysergic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Butler, A., Hill, J. M., Ireland, S. J. and Tyers, M. B. (1988). Pharmacological properties of GR 38032F, a novel antagonist at 5-HT3 receptors. Br. J. Pharmacol., 94, 397–412.Google Scholar
  2. Costall, B., Domeney, A. M., Kelly, M. E., Naylor, R. J. and Tyers, M. B. (1987a). The antipsychotic potential of GR 38032F, a selective antagonist of 5-HT3receptors in the central nervous system. Br. J. Pharmacol., 90, 89PGoogle Scholar
  3. Costall, B., Domeney, A. M., Naylor, R. J. and Tyers, M. B. (1987b). Effects of the 5-HT3 receptor antagonist, GR 38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain. Br. J. Pharmacol., 92, 881–894Google Scholar
  4. Costall, B., Hendrie, C. A., Kelly, M. E. and Naylor, R. J. (1987c). Actions of sulpiride and tiapride in a simple model of anxiety in mice. Neuropharmacology, 26, 195–200Google Scholar
  5. Elliott, P., Alpert, J. E., Bannon, M. J. and Iversen, S. D. (1986). Selective activation of mesolimbic and mesocortical dopamine metabolism in rat brain by infusion of a stable substance P analogue into the ventral tegmental area. Brain Res., 363, 145–147Google Scholar
  6. Fake, C. S., King, F. D. and Sanger, G. J. (1987). BRL 43694: a potent and novel 5-HT3 receptor antagonist. Br. J. Pharmacol., 91, 335PGoogle Scholar
  7. Fozard, J. R. (1984). MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn-Schmiedeberg’s Arch. Pharmacol., 326, 36–44Google Scholar
  8. Hagan, R. M., Butler, A., Hill, J. M., Jordan, C. C., Ireland, S. J. and Tyers, M. B. (1987). Effect of the 5-HT3 receptor antagonist GR 38032F, on responses to injection of a neurokinin agonist into the ventral tegmental area of the rat brain. Eur. J. Pharmacol., 138, 303–305Google Scholar
  9. Ireland, S. J. and Tyers, M. B. (1987). Pharmacological characterisation of 5-hydroxytryptamine-induced depolarisation of the rat isolated vagus nerve. Br. J. Pharmacol., 90, 229–238Google Scholar
  10. Jones, B. J., Oakley, N. R. and Tyers, M. B. (1987). The anxiolytic activity of GR 38032F, a 5-HT3 receptor antagonist, in the rat and Cynomolgus monkey. Br. J. Pharmacol., 90, 88PGoogle Scholar
  11. Jones, B. J., Costall, B., Domeney, A. M., Kelly, M. E., Naylor, R. J., Oakley, N. R. and Tyers, M. B. (1988). The potential anxiolytic activity of GR 38032F, a 5-HT3 receptor antagonist. Br. J. Pharmacol., 93, 985–993Google Scholar
  12. Kilpatrick, G. J., Jones, B. J. and Tyers, M. B. (1987). Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature, 330, 746–748Google Scholar
  13. Peroutka, S. J. and Snyder, S. H. (1979). Multiple serotonin receptors: differential binding of [3H]-5-hydroxytryptamine, [3H]-lysergic acid diethylamide and [3H]-spiroperidol. Mol. Pharmacol., 16, 687–699Google Scholar
  14. Peroutka, S. J., Lebovitz, R. M. and Snyder, S. H. (1981). Two distinct central serotonin receptors with different physiological functions. Science, 212, 827–829Google Scholar
  15. Richardson, B. P., Engel, G., Donatsch, P. and Stadler, P. A. (1985). Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature, 316, 126–131Google Scholar
  16. Tyers, M. B., Costall, B., Domeney, A. M., Jones, B. J., Kelly, M. E., Naylor, R. J. and Oakley, N. R. (1987). The anxiolytic activities of 5-HT3 antagonists in laboratory animals. Neurosci. Lett., Suppl. 29, S68Google Scholar

Copyright information

© The editors and contributors 1989

Authors and Affiliations

  • M. B. Tyers
    • 1
  • B. Costall
    • 2
  • R. J. Naylor
    • 2
  1. 1.Neuropharmacology DepartmentGlaxo Group Research LimitedWareUK
  2. 2.Postgraduate School of Studies in PharmacologyUniversity of BradfordBradfordUK

Personalised recommendations