Autoradiographic Studies of Serotonin Receptors

  • J. M. Palacios
  • M. M. Dietl
Part of the The Receptors book series (REC)


Our perception of the chemical organization of the brain has been dramatically modified in the last 20 years by the results of the application of techniques such as histofluorescence, immuno-histochemistry, and autoradiography to the study of neurotransmitters. Serotonin has not been an exception but, rather, a forerunner. Serotonergic pathways have been studied using fluorescence microscopy, autoradiography, and immunohistochemistry. In 1964 Dahlström and Fuxe described the distribution of the serotoninergic cell bodies using the fluorescence technique of Falck et al. (1962). Autoradiography has been extensively used by Descarries and collaborators (Beaudet and Descarries, 1978; Parent et al., 1981) to trace 5-HT pathways. Finally, the development of antibodies has opened a new era in the research of 5-HT neurons in the brain, and allowed detailed investigation at the light- and electron-microscopic levels (Steinbush, 1981). More recently, these anatomical studies have been extended to the localization of receptor sites for this neurotransmitter.


Dentate Gyrus Choroid Plexus Serotonin Receptor Globus Pallidus Autoradiographic Study 
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  1. Beaudet, A. and Descarries, L. (1978) The monoamine innvervation of rat cerebral cortex: synaptic and non-synaptic axon terminals. Neurosci. 3, 851–860.CrossRefGoogle Scholar
  2. Biegon, A., Kargman, S., Snyder, L., and McEwen, B. S. (1986) Characterization and localization of serotonin receptors in human brain postmortem. Brain Res. 363, 91–98.PubMedCrossRefGoogle Scholar
  3. Bird, E. D. and Iversen, L. L. (1982) Human brain postmortem studies of neurotransmitters and related markers. In Handbook of Neurochemistry (A. Lajtha, ed.), vol. 2, Plenum, New York, pp. 225–251.Google Scholar
  4. Branchek, T., Kates, M., and Gershon, M. D. (1984) Enteric receptors for 5-hydroxytryptamine. Brain Res. 324, 107–118.PubMedCrossRefGoogle Scholar
  5. Closse, A. (1983) [3H]mesulergine, a selective ligand for serotonin-2 receptors. Life Sci. 32, 2485–2495.Google Scholar
  6. Conn, P. J., Hanowsky, A., and Sanders-Bush, E. (1987) Denervation supersensitivity of 5-HT1C receptors in rat charoid plexus. Brain Res. 400, 396–398.PubMedCrossRefGoogle Scholar
  7. Cross, A.J. (1982) Interaction of 3HLSD with serotonin receptors in human brain. Eur. J. Pharmacol. 82, 77–80.PubMedCrossRefGoogle Scholar
  8. Dahlström, A. and Fuxe, K. (1964) Evidence of the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brainstem neuron. Acta Physiol. Scand. 62, Suppl. 232, 1–55.Google Scholar
  9. Dietl, M. and Palacios, J. M. (1988) Receptor autoradiography as a tool for the study of the phylogeny of the basal ganglia. J. Rec. Res., in press.Google Scholar
  10. Engel, G., Wagner, O., and Wagner, H. (1980) Radioreceptor assay for the determination of β-adrenoceptor blocking agents in blood and brain of rats. Experientia 36, 706.Google Scholar
  11. Engel, G., Müller-Schweinitzer, E., and Palacio, J. M. (1984) 2-[125Iodo] LSD, a new ligand for the characterization and localization of 5-HT2 receptors. Naunyn Schmiedeberg’s Arch. Pharmacol. 325, 328–336.CrossRefGoogle Scholar
  12. Enna, S. J., Bennett, J. P., Bylund, D. B., Creese, I., Burt, D. R., Charness, M. E., Yamamura, H. I., Simantov, R., and Snyder, S. H. (1977) Neurotransmitter receptor binding: regional distribution in human brain. J. Neurochem. 28, 233–236.PubMedCrossRefGoogle Scholar
  13. Euvrard, C. and Boissier, J. R. (1980) Biochemical assessment of the central 5-HT agonist activity of RU-24 969 (a piperidinylindole). Eur. J. Pharmacol. 63, 65–72.PubMedCrossRefGoogle Scholar
  14. Falck, B., Hipparp, N. A., Thieme, G., and Torp, A. (1962) Fluorescence of catecholamines and related compounds with formaldehyde. J. Histochem. Cytochem. 10, 348–354.CrossRefGoogle Scholar
  15. Fischette, C. T., Biegon, A., and McEwen, B. S. (1983) Sex differences in serotonin-1 receptor binding in rat brain. Science 222, 333–335.PubMedCrossRefGoogle Scholar
  16. Gaddum, J. H. and Picarelli, Z. P. (1957) Two kinds of tryptamine receptor. Brit. J. Pharmacol. 12, 323–328.PubMedGoogle Scholar
  17. Glaser, T., Rath, M., Traber, J., Zilles, K., and Schleicher, A. (1985) Autoradiographic identification and topographical analyses of high affinity serotonin receptor subtypes as a target for the novel putative anxiolytic TVX-Q 7821. Brain Res. 358, 129–136.PubMedCrossRefGoogle Scholar
  18. Gozlan, H., El Mestikawy, S., Pichat, L., Glowinski, J and Hamon, M. (1983) Identification of presynaptic serotonin autoreceptors using a new ligand: [3H]PAT. Nature 305, 140–142.PubMedCrossRefGoogle Scholar
  19. Heuring, R. E. and Peroutka, S. J. (1987) Characterization of a novel [3H]5-hydroxytryptamine binding site subtype in bovine brain membranes. J. Neurosci. 7, 894–903.PubMedGoogle Scholar
  20. Hoyer, D., Pazos, A., Probst, A., and Palacios, J. M. (1986a) 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.PubMedCrossRefGoogle Scholar
  21. Hoyer, D., Pazos, A., Probst, A., and Palacios, J. M. (1986b) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res. 376, 97–107.PubMedCrossRefGoogle Scholar
  22. Hoyer, D., Waeber, C., Pazos, A., Probst, A., and Palacios, J. M. (1988) Identification of a 5-HT1 recognition site in human brain membranes different from 5-HT1A, 5-HT1B and 5-HT1C sites. Neurosci. Letters 85, 357–362.CrossRefGoogle Scholar
  23. Köhler, C., Radesater, A.-C., Lang, W., and Chan-Palay, V. (1986) Distribution of serotonin-1A receptors in the monkey and the postmortem human hippocampal region. A quantitative autoradiographic study using the selective agonist [3H]8-OH-DPAT. Neurosci. Lett. 72, 43–48.PubMedCrossRefGoogle Scholar
  24. Kuhar, M. J. (1985) Receptor localization with the microscope. In Neurotransmitter Receptor Binding, 2nd ed. (H. I. Yamamura, ed.) Raven, New York, pp. 153–180.Google Scholar
  25. Leysen, J. E., Niemegeers, C. J. E., Tollenaere, J. P., and Laduron, P. M. (1978) Serotonergic component of neuroleptic receptors. Nature 272, 168–171.PubMedCrossRefGoogle Scholar
  26. Leysen, J. E., Niemegeers, C. J. E., Van Nueten, J. M., and Laduron, P. M. (1982) [3H]ketanserin (R 41 468), a selective [3H]-ligand for serotonin2 receptor binding sites. Mol. Pharmacol. 21, 301–314.PubMedGoogle Scholar
  27. Marcinkiewicz, M., Vergé, D., Gozlan, H., Pichat, L., and Hamon, M. (1984) Autoradiographic evidence for the heterogeneity of 5-HT1 sites in the rat brain. Brain Res. 291, 159–163.PubMedCrossRefGoogle Scholar
  28. Meibach, R. C., Maayani, S., and Green, J. P. (1980) Characterization and radioautography of [3H]LSD binding by rat brain slices in vitro: the effect of 5-hydroxytryptamine. Eur. J. Pharmacol. 67, 371–382.PubMedCrossRefGoogle Scholar
  29. Palacios, J. M., Niehoff, D. L., and Kuhar, M. J. (1981) Receptor autoradiography with tritium-sensitive film: potential for computerized densitometry. Neurosci. Lett. 24, 111–116.CrossRefGoogle Scholar
  30. Palacios, J. M., Probst, A., and Cortér, R. (1983) The distribution of serotonin receptors in the human brain: high density of [3H]-LSD binding sites in the raphé nuclei of the brain stem. Brain Res. 274, 150–155.PubMedCrossRefGoogle Scholar
  31. Parent, A., Descarries, L., and Beaudet, A. (1981) Organization of ascending serotonin systems in the adult rat brain. A radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine. Neurosci. 6, 115–138.CrossRefGoogle Scholar
  32. Pazos, A., Hoyer, D., and Palacios, J. M. (1984a) Mesulergine, a selective serotonin-2 ligand in the rat cortex, does not label these receptors in porcine and human cortex: evidences for species differences on brain serotonin-2 receptors. Eur. J. Pharmacol. 106, 531–538.PubMedCrossRefGoogle Scholar
  33. Pazos, A., Hoyer, D., and Palacios, J. M. (1984b) The binding of serotoninergic ligand to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur. J. Pharmacol. 106, 539–546.PubMedCrossRefGoogle Scholar
  34. Pazos, A., Engel, G., and Palacios, J. M. (1985a) β-Adrenoceptor blocking agents recognize a subpopulation of serotonin receptors in brain. Brain Res. 343, 403–408.PubMedCrossRefGoogle Scholar
  35. Pazos, A., Cortés, R., and Palacios, J. M. (1985b) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors. Brain Res. 346, 231–249.PubMedCrossRefGoogle Scholar
  36. Pazos, A. and Palacios, J. M. (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res. 346, 205–230.PubMedCrossRefGoogle Scholar
  37. Pazos, A., Probst, A., and Palacios, J. M. (1987a) Serotonin receptors in the human brain. III. Autoradiographic mapping of serotonin-1 receptors. Neurosci. 21, 97–122.CrossRefGoogle Scholar
  38. Pazos, A., Probst, A., and Palacios, J. M. (1987b) Serotonin receptors in the human brain. IV. Autoradiographic mapping of serotonin-2 receptors. Neurosci. 21, 123–139.CrossRefGoogle Scholar
  39. Penney, J. B., Pan, H. S., Young, A. B., Frey, K. A., and Dauth, G. W. (1981) Quantitative autoradiography of [3H]muscimol binding in rat brain. Science 214, 1036–1038.PubMedCrossRefGoogle Scholar
  40. 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, 687–699.PubMedGoogle Scholar
  41. Quirion, R. and 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.PubMedCrossRefGoogle Scholar
  42. 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, 126–131.PubMedCrossRefGoogle Scholar
  43. Richardson, B. P. and Engel, G. (1986) The pharmacology and function of 5-HT3 receptors. TINS 9, 424–428.Google Scholar
  44. Rochae Silva, M., Valle, J. R., and Picarelli, Z. P. (1953) Pharmacological analysis of the mode of action of serotonin (5-hydroxytryptamine) upon the guinea-pig ileum. Br. J. Pharmacol. 8, 378–388.Google Scholar
  45. Schotte, A., Maloteaux, J. M., and Laduron, P. M. (1983) Characterization and regional distribution of serotonin-S2 receptors in human brain. Brain Res. 276, 231–235.PubMedCrossRefGoogle Scholar
  46. Segu, L., Abdelkefi, J., Dusticier, G., and Lanoir, J. (1986) High-affinity serotonin binding sites: autoradiographic evidence for their location on retinal afferents in the rat superior colliculus. Brain Res. 384, 205–217.PubMedCrossRefGoogle Scholar
  47. Steinbush, H. W. M. (1981) Distribution of serotonin-immunoreactivity in the central nervous system of the rat — cell bodies and terminals. Neurosci. 6, 557–618.CrossRefGoogle Scholar
  48. Stumpf, W. E. and Roth, L. G. (1966) High resolution autoradiography with dry-mounted, freeze-dried frozen sections: comparative study of six methods using two diffusible compounds, [3H]estradiol and [3H]mesobilirubinogen. J. Histochem. Cytochem. 14, 274–287.PubMedCrossRefGoogle Scholar
  49. Traber, J., Davies, M. A., Dompert, W. U., Glaser, T., Schuurman, T., and Seidel, P.-R. (1984) Brain serotonin receptors as a target for the putative anxiolytic TVX-Q 7821. Brain Res. Bull. 12, 741–744.PubMedCrossRefGoogle Scholar
  50. Unnerstall, J. R., Niehoff, D. L., Kuhar, M. J., and Palacios, J. M. (1982) Quantitative receptor autoradiography using [3H]Ultrofilm: application to multiple benzodiazepine receptors. J. Neurosci. Meth. 6, 59–73.CrossRefGoogle Scholar
  51. Uphouse, L., Williams, J., Eckols, K., and Sierra, V. (1986) Variations in binding of [3H]5-HT to cortical membranes during the female rat estrous cycle. Brain Res. 381, 376–381.PubMedCrossRefGoogle Scholar
  52. Vergé, D., Daval, G., Patay, A., Gozlan, H., El Mestikawy, S., and Hamon, M. (1985) Presynaptic 5-HT autoreceptors on serotoninergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur. J. Pharmacol. 113, 463–464.PubMedCrossRefGoogle Scholar
  53. Vergé, D., Daval, G., Marcinkiewicz, M., Patey, A., El Mestikawy, S., Gozlan, H., and Hamon, M. (1986) Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5,7-dihydroxytryptamine-treated rats. J. Neurosci. 6, 3474–3482.PubMedGoogle Scholar
  54. Waeber, C., Dietl, M. M., Hoyer, D., Probst, A., and Palacios, J. M. (1988) Visualization of a novel serotonin recognition site (5-HT-1D) in the human brain by autoradiography. Neurosci. Letters, in press.Google Scholar
  55. Weissmann-Nanopoulos, D., Mach, E., Magre, J., Demassey, Y., and Pujol, J.-F. (1985) Evidence for the localization of 5-HT1A binding sites on serotonin containing neurons in the raphé dorsalis and raphé centralis nuclei of the rat brain. Neurochem. Int. 7, 1061–1072.PubMedCrossRefGoogle Scholar
  56. Weissman, D., Mach, E., Oberlander, C., Demassey, Y., and Pujol, J.-F. (1986) Evidence for hyperdensity of 5-HT1B binding sites in the substantia nigra of the rat after 5,7-dihydroxytryptamine intraventricular injection. Neurochem. Int. 9, 191–200.CrossRefGoogle Scholar
  57. Yagaloff, K. A. and Hartig, P. R. (1985) [125I]lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells. J. Neurosci. 12, 3178–3183.Google Scholar
  58. Young, W. S., III, and Kuhar, M. J. (1979) A new method for receptor autoradiography [3H]opioid receptor labeling in mounted tissue sections. Brain Res. 179, 255–270.PubMedCrossRefGoogle Scholar
  59. Young, W. S. and Kuhar, M. J. (1980) Serotonin receptor localization in rat brain by light microscopic autoradiography. Eur. J. Pharmacol. 62, 237–239.PubMedCrossRefGoogle Scholar

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© The Humana Press Inc. 1988

Authors and Affiliations

  • J. M. Palacios
  • M. M. Dietl

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