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5.HT1 receptors in the vertebrate brain

Regional distribution examined by autoradiography


The regional distribution of high affinity [33H]5-HT recognition sites in the brain of several vertebrates (pigeon, rat, mouse, guinea-pig, cat, dog, monkey and human) was analyzed using in vitro autoradiography. The presence of subtypes of 5-HT1 binding sites was investigated by selective displacements with 8-OH-DPAT, mesulergine and (±)SDZ 21-009 at appropriate concentrations to block 5-HT1A, 5-HT1c and 5-HT1B sites respectively. In addition, 5-HT1A, and 5-HT1c sites were directly visualized with the more selective radioligands [3H]8-OH-DPAT and [3H]mesulergine, respectively. In the pigeon brain, total [3H]5-HT binding sites were enriched in all telencephalic areas. Densely labelled regions were also present in the optic tectum and the brainstem. No binding was observed in the cerebellum. 8-OH-DPAT and mesulergine only displaced a small proportion of [3H]5-HT binding in most of the areas where high concentrations of 5-HT1 sites were found. (±)SDZ 21-009 did not affect [3H]5-HT binding in the regions examined. Taking into account our pharmacological studies, these results suggest that the majority of 5-HT1 sites belong to the 5-HT1D subtype in the pigeon brain. In the mammalian species investigated high levels of [3H]5-HT binding were found in the neo-cortex, hippocampal formation, basal ganglia and related structures (substantia nigra), raphe dorsalis, nucleus superior colliculus and choroid plexus. However, these brain areas were differentially enriched in subtypes of 5-HT1 recognition sites. 5-HT1A sites were observed in the neo-cortex, the hippocampal formation and the raphe nucleus, whereas 5-HT1C sites accounted for all 5-HT1 binding in the choroid plexus. In the mouse and rat brain, 5-HT1B binding sites were enriched in the basal ganglia and associated regions (substantia nigra). These areas were enriched in 5-HT1D sites in the brain of the other mammals studied. In these animals, no site with a 5-HT1B pharmacological profile were detected.

These results indicate that 5-HT1A 5-HT1c and 5-HT1D sites are present already in the lower vertebrate species investigated and that 5-HT1B appear to be exclusive of the myomorph rodents (mouse, rat). Furthermore, the different subtypes of the 5-HT1, receptors present a conserved regional distribution with the 5-HT1D sites being enriched in the basal ganglia and the 5-HT1A sites predominating in the hippocampal formation.

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  1. Bouhelal R, Smounya L, Bockaert J (1988) 5-HT1B receptors are negatively coupled with adenylate cyclase in rat substantia nigra. Eur J Pharmacol 151:189–196

  2. Brauth SE, Kitt CA (1980) The palcostriatal system of Caiman crocodilus. J Comp Neurol 189:437–465

  3. Brauth SE, Fergusson JL, Kitt CA (1978) Prosencephalic pathways related to the paleostriatum of the pigeon (Columbia Livia). Brain Res 147:205–221

  4. Campos MF, Rodrigues FC (1987) Rats and marmosets respond differently to serotonin agonists and antagonists. Psychopharmacology 92:478–483

  5. Dietl MM, Palacios JM (1988) Receptor autoradiography as a tool for the study of the phylogeny of the basal ganglia. J Receptor Res 8:521–532

  6. Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg's Arch Pharmacol 332:1–7

  7. Galzin AM, Blier P, Chodkiewicz JP, Poirier MF, Loo H, Roux FX, Redondo A, Lista A, Ramdine R, Langer SZ (1988) Pharmacological characterization of the serotonin 5-HT autoreceptor modulating the electrically-evoked release of 3H-5-HT from slices of human frontal cortex. Soc Neurosci vol 14:129.7 (Abstracts)

  8. Gerschenfeld HM, Paupardin-Tritsch D (1974) Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine. J Physiol (Lond) 243:427–456

  9. Heuring RE, Schlegel JR, Peroutka SJ (1986) Species variations in RU 24969 interactions with non 5-HT1A binding sites. Eur J Pharmacol 122:279–282

  10. Hoyer D, Engel G, Kalkman HO (1985a) Characterization of the 5-HT1B recognition site in rat brain: binding studies with (−) [125I]iodocyanopindolol. Eur J Pharmacol 118:1–12

  11. Hoyer D, Engel G, Kalkman HO (1985 b) Molecular pharmacology of 5-HT1B, and 5-HT2 recognition sites in rat and pig brain membranes: Radioligand binding studies with [3H]5-HT, [3H]8 OH-DPAT, (−)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserine. Eur J Pharmacol 118:13–23

  12. Hoyer D, Pazos A, Probst A, Palacios JM (1986) Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res 376:85–96

  13. Jonsson G (1981) Lesion methods in neurobiology in: Heym C, Forssmann W-G (eds) Techniques in neuroanatomical research. Springer, Berlin Heidelberg New York, pp 71–99

  14. Middlemiss DN, Bremer ME, Smith SM (1988) A pharmacological analysis of the 5-HT receptors mediating inhibition of 5-HT release in the guinea-pig frontal cortex. Eur J Pharmacol 157:101–107

  15. Murphy TL Bylund DB (1988) Oxymetazoline inhibits adenylate cyclase by activation of serotonin-1 receptors in the OK cell, an established renal epithelial cell line. Mol Pharmacol 34:1–7

  16. Oberlander C, Blaquière B, Pujol J-F (1986) Distinct functions for dopamine and serotonin in locomotor behavior: evidence using the 5-HT1, agonist RU 24969 in globus pallidus-lesioned rats. Neurosci Lett 67:113 -118

  17. Palacios JM, Died MM (1989) Autoradiographic studies on 5-HT receptors in: Sanders-Bush (ed) The serotonin receptors. The Humana Press Inc, Clifton New Jersey, pp 89–138

  18. Palacios JM, Pazos A, Hoyer D (1987) Characterization and mapping of 5-HTIA sites in the brain of animals and man. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors, Horwood, Chichester, pp 67–81

  19. Parent A (1973) Demonstration of a catecholaminergic pathway from the midbrain to the strioamygdaloid complex in the turtle (Chrysemys Picta). J Anat 114:379–387

  20. Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain 1: Serotonin-1 receptors. Brain Res 346:205–230

  21. Pazos A, Probst A, Palacios JM (1987) Serotonin receptors in the human brain III Autoradiographic mapping of serotonin-1 receptors. Neuroscience 21:97–122

  22. Pazos A, Hoyer D, Died MM, Palacios JM (1988) Autoradiography of serotonin receptors. In: Osborne NN, Hamon M (eds) Neuronal serotonin. Wiley, New York, p 507–543

  23. Peroutka SJ (1988) 5-hydroxytryptamine receptor subtypes: molecular, biochemical and physiological characterization. TINS 11:496–500

  24. Quirion R, Richard J (1987) Differential effects of selective lesions of cholinergic and dopaminergic neurons on serotonin type 1 receptors in rat brain. Synapse 1:124–130

  25. Reiner A, Brauth SE, Karten HJ (1984) Evolution of the amniote basal ganglia. TINS 7:320–325

  26. Schlicker E, Fink K, Betz R, Göthert M (1988) The serotonin autoreceptor in the pig brain cortex belongs to the 5-HTID receptor subtype. Naunyn-Schmiedeberg's Arch Pharmacol 338 (suppl): R67

  27. Schnellmann RG, Waters SJ, Nelson DL (1984) [3H]5-hydroxytryptamine binding sites: species and tissue variations. J Neurochem 42:65–70

  28. Schoeffter P, Waeber C, Palacios JM, Hoyer D (1988) The 5hydroxytryptamine 5-HTID receptor is negatively coupled to adenylate cyclase in rat substantia nigra. Naunyn-Schmiedeberg's Arch Pharmacol 337:602–608

  29. Schwarcz R, Bennett JP, Coyle JT (1977) Loss of striatal serotonin synaptic receptor binding induced by kainic acid lesions: correlations with Huntington's disease. J Neurochem 28:867–869

  30. Schwartz JH, Shkolnik LJ (1981) The giant serotoninergic neuron in Aplysia: a multi-targeted nerve cell. J Neurosci 1:606–619

  31. Seuwen K, Magnaldo I, Pouysségur J (1988) Serotonin stimulates DNA synthesis in fibroblasts acting through 5-HTIB receptors coupled to a Gi-protein. Nature 335:254–256

  32. Smeets WJAJ, Hoogland PV, Voorn P (1986) The distribution of dopamine immunoreactivity in the forebrain and midbrain of the lizard Gekko gecko: an immunohistochemical study with antibodies against dopamine. J Comp Neurol 253:46–60

  33. Smith GN, Hingtgen J, DeMyer W (1987) Serotonergic involvement in the backward tumbling response of the parlor tumbler pigeon. Brain Res 400:399–402

  34. Waeber C, Schoeffter P, Palacios JM, Hoyer D (1988 a) Molecular pharmacology of 5-HT1D recognition sites: radioligand binding studies in human, pig and calf brain membranes. Naunyn-Schmiedeberg's Arch Pharmacol 337:595–601

  35. Waeber C, Died MM, Hoyer D, Probst A, Palacios JM (1988b) Visualization of a novel serotonin recognition site (5-HT1D) in the human brain by autoradiography. Neurosci Lett 88:11–16

  36. Waeber C, Schoeffter P, Palacios JM, Hoyer D (1989) 5-HT1D receptors in guinea-pig and pigeon brain: radioligand binding and biochemical studies. Naunyn-Schmiedeberg's Arch Pharmacol 340:479–485

  37. Waeber C, Palacios JM (1989) Serotonin-1 receptors in the human basal ganglia are decreased in Huntington's chorea but not in Parkinson's disease. Neuroscience (in press)

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Correspondence to C. Waeber.

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Waeber, C., Died, M.M., Hoyer, D. et al. 5.HT1 receptors in the vertebrate brain. Naunyn-Schmiedeberg's Arch Pharmacol 340, 486–494 (1989).

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Key words

  • Serotonin
  • [3H]5-HT
  • 5-HT1B and 5-HT1D sites
  • Autoradiography
  • Species differences
  • Basal ganglia