Effects of Acute and Chronic Treatment with Imipramine on 5-Hydroxytryptamine and 5-Hydroxytryptamine Comodulators in Central 5-Hydroxytryptamine Neurons and on Glucocorticoid Receptors in Central Monoaminergic Neurons: a Morphometrical and Microdensitometrical Analysis

  • K. Fuxe
  • I. Kitayama
  • A. M. Janson
  • L. F. Agnati
  • A. Cintra
  • S. O. Ögren
  • A. Härfstrand
  • P. Eneroth
  • J.-Å Gustafsson
Chapter

Abstract

Central 5-hydroxytryptamine (5-HT) neurons represent targets of action for antidepressant drugs, as for example is demonstrated by the presence of high densities of [3H]-imipramine binding sites in the nerve cell membranes of the central 5-HT neurons (see Langer and Briley, 1981). Quantitative receptor auto-radiography of [3H] -imipramine binding sites has indicated their presence in the nerve cell membrane of the 5-HT cell bodies, axons and nerve terminals (Fuxe et al., 1983a). The density of [3H]-imipramine binding sites seems particularly high in the 5-HT nerve cell group of the nucleus raphe dorsalis (group B7; Dahlström and Fuxe, 1964). In view of the fact that a high secretion of cortisol has been demonstrated in patients with a severe depression (see Carroll, 1984), it is also of particular interest that strong glucocorticoid receptor (GR) immunoreactivity (IR) has been demonstrated in the vast majority of the 5-HT nerve cells of the lower brain-stem of the male rat (Fuxe et ah, 1985a, b; Härfstrand et al., 1986a).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agnati, L.F., Benfenati, F., Cortelli, P., and D’Alessandro, R. (1978). A new method to quantify catecholamine stores visualized by means of the Falck-Hillarp technique. Neurosci. Lett., 10, 11–17.CrossRefPubMedGoogle Scholar
  2. Agnati, L.F., Fuxe, K., Locatelli, V., Benfenati, F., Zini, I., Panerai, A.E., El Etreby, M.F., and Hökfelt, T. (1982). Neuroanatomical methods for the quantitative evaluation of coexistence of transmitters in nerve cells. Analysis of the ACTH-and beta-endorphin immunoreactive nerve cell bodies of the mediobasal hypothalamus of the rat. J. Neuro-sci. Methods, 5, 203–14.CrossRefGoogle Scholar
  3. Agnati, L.F., Fuxe, K., Benfenati, F., Zini, I., and Hökfelt, T. (1983). On the functional role of coexistence of 5-HT and substance P in bulbospinal 5-HT neurons. Substance P reduces affinity and increases density of 3H-5-HT binding sites. Acta Physiol Scand., 117, 299–301.CrossRefPubMedGoogle Scholar
  4. Agnati, L.F., Fuxe, K., Benfenati, F., Zini, I., Zoli, M., Fabbri, L., and Härfstrand, A. (1984). Computer assisted morphometry and microdensitometry of transmitter identified neurons with special reference to the mesostriatal dopamine pathway. I. Methodological aspects. Acta Physiol Scand., 120, 621–4.CrossRefPubMedGoogle Scholar
  5. Agnati, L.F., and Fuxe, K. (1985). Quantitative Neuroanatomy in Transmitter Research, Macmillan, Basingstoke.Google Scholar
  6. Agnati, L.F., Fuxe, K., Zoli, M., Zini, I., Härfstrand, A., Toffano, G., and Goldstein, M. (subm.). Morphometrical and microdensitometrical studies on phenylethanolamine-N-methyltransferase and neuropeptide γ-immunoreactive neurons in the rostral medulla oblongata of the adult and old male rat. Neuroscience.Google Scholar
  7. Björklund, A.J., Emson, P.C, and Gilbert, R.F.T. (1979). Further evidence for the possible coexistence of 5-hydroxytryptamine and substance P in medullary raphe neurones of rat brain. Br. J. Pharmacol, 66, 112–13.Google Scholar
  8. Blier, P., and de Montigny, C. (1980). Effect of chronic tricyclic antidepressant treatment on the serotoninergic autoreceptor. A microiontophoretic study in the rat. Naunyn Schmiedeberg’s Arch. Pharmacol, 314, 123–8.CrossRefGoogle Scholar
  9. Brodin, E., Peterson, L-L., Ögren, S-O., and Bartfai, T. (1984). Chronic treatment with serotonin uptake inhibitor zimelidine elevates substance P levels in the rat spinal cord. Acta Physiol Scand., 122, 209–11.CrossRefPubMedGoogle Scholar
  10. Carlsson, A., and Lindqvist, M. (1978). Effects of antidepressant agents on the synthesis of brain monoamines. J. Neural Transm., 43, 73–91.CrossRefPubMedGoogle Scholar
  11. Carroll, B.J. (1984). Dexamethasone suppression test for depression. In Advances in Biochemical Psychopharmacology, vol. 39, Raven, New York, 179–88.Google Scholar
  12. Cintra, A., Fuxe, K., Härfstrand, A., Agnati, L.F., Miller, L.S., Greene, J.L., and Gustafsson, J.-Å. (1986). On the cellular localization and distribution of estrogen receptors in the rat tel-and diencephalon using monoclonal antibodies to human estrogen receptor. Neurochem. Int., 8, 585–95.CrossRefGoogle Scholar
  13. Corrodi, H., and Fuxe, K. (1969). Decreased turnover in central 5-HT nerve terminals induced by antidepressant drugs of the imipramine type. Eur. J. Pharmacol, 7, 56–9.Google Scholar
  14. Dahlström, A., and Fuxe, K. (1964). Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brainstem neurons. Acta Physiol. Scand., 62, 1–55.Google Scholar
  15. Dahlström, A., and Fuxe, K. (1965). Evidence for the existence of monoamine containing neurons in the central nervous system. II. Experimentally induced changes in the intra-neuronal amine levels. Acta Physiol Scand., 64, 1–36.CrossRefGoogle Scholar
  16. de Montigny, C, and Blier, P. (1984). Effects of antidepressant treatments on 5-HT neurotransmission: Electrophysiological and clinical studies. Adv. Biochem. Psychopharmacol., 39, 223–41.PubMedGoogle Scholar
  17. Fuxe, K., Hökfelt, T., and Ungerstedt, U. (1970). Morphological and functional aspects of central monoamine neurons. International Review of Neurobiology. Academic, New York, 13, 93–126.CrossRefGoogle Scholar
  18. Fuxe, K., Calza, L., Benfenati, F., Zini, I., and Agnati, L.F. (1983a). Quantitative autoradio-graphic localization of 3H-imipramine binding sites in the brain of the rat: Relationship to ascending 5-hydroxytryptamine neuron systems. Proc. Natl Acad. Sci., 80, 3836–40.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Fuxe, K., Agnati. L. F., Andersson, K., Calza, L., Benfenati, F., Zini, M., Battistini, N., Köhler, C, Ögren, S.-O., and Hökfelt, T. (1983b). In Ackenheil, M., and Matussek, N. (eds.), Special Aspects of Psychopharmacology, Expansion Scientifique Française, Paris, 13–32.Google Scholar
  20. Fuxe, K., Ögren, S.-O., Benfenati, F., and Agnati, L.F. (1984). In Usdin, E., Åsberg, M., Bertilsson, L., and Sjöqvist, F. (eds.), Frontiers in Biochemical and Pharmacological Research in Depression, Raven, New York, 271–84.Google Scholar
  21. Fuxe, K., Wikström, A.-C, Okret, S., Agnati, L.F., Härfstrand, A., Yu, Z.-Y., Granholm, L., Zoli, M., Vale, W., and Gustafsson, J.-A. (1985a). Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel-and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor. Endocrinology, 177, 1803–12.Google Scholar
  22. Fuxe, K., Härfstrand, A., Agnati, L.F., Yu, Z.-Y., Cintra, A., Wikström, A.-C, Okret, S., Cantoni, E., and Gustafsson, J.-Å. (1985b). Immunocytochemical studies on the localization of glucocorticoid receptor immunoreactive nerve cells in the lower brain stem and spinal cord of the male rat using a monoclonal antibody against rat live glucocorticoid receptor. Neurosci. Lett., 60, 1–6.CrossRefPubMedGoogle Scholar
  23. Fuxe, K., Agnati, L.F., Zoli, M., Härfstrand, A., Grimaldi, R., Bernardi, P., Camurri, M., and (1985c). In Agnati, L.F., and Fuxe, K. (eds.), Quantitative Newoanatomy in Transmitter Research, Macmillan, Basingstoke, 331–48.Google Scholar
  24. Fuxe, K., Agnati, L.F., Zoli, M., Härfstrand, A., Grimaldi, R., Bernardi, P., Camurri, M. and Goldstein, M. (1985d). In Agnati, L.F., and Fuxe, K. (eds.), Quantitative Neuroanatomy in Transmitter Research, Macmillan, Basingstoke, 157–74.Google Scholar
  25. Hallman, H., Jonsson, G. and Sundström, E. (1984). Effects of the noradrenaline neuro-toxin DSP4 on monoamine neurons and their transmitter turnover in rat CNS. J. Neural Transm., 60, 89–102.CrossRefPubMedGoogle Scholar
  26. Härfstrand, A., Fuxe, K., Cintra, A., Agnati, L.F., Zini, I., Wikström, A.-C., Okret, S., Yu, Z.–Y., Goldstein, M., Steinbusch, H., Verhofstad, A., and Gustafsson, J.-Å. (1986a). Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain. Proc. Natl Acad. Sci., 83, 9779–83.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Härfstrand, A., Fuxe, K., Agnati, L.F., Eneroth, P., Zini, I., Zoli, M., Andersson, K., von Euler, G., Terenius, L., Mutt, V., and Goldstein, M. (1986b). Studies on neuropeptide γ-catecholamine interactions in the hypothalamus and in the forebrain of the male rat. Relationship to neuroendocrine function. Neurochem. Int., 8, 355–76.CrossRefPubMedGoogle Scholar
  28. Hökfelt, T., Ljungdahl, Å., Steinbusch, H., Verhofstad, A., Nilsson, G., Brodin, E., Pernow, B., and Goldstein, M. (1978). Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system. Neuroscience, 3, 517–38.CrossRefPubMedGoogle Scholar
  29. Iverfeldt, K., Peterson, L.-L., Brodin, E., Ögren, S.-O., and Bartfai, T. (1986). Serotonin type-2 receptor mediated regulation of substance-P release in the ventral spinal cord and the effects of chronic antidepressant treatment. Arch. Pharmacol., 333, 1–6.CrossRefGoogle Scholar
  30. Johansson, O., Hökfelt, T., Pernow, B., Jeffcoate, S.L., White, N., Steinbusch, H.W.B., Verhofstad, A.A.L., Emson, P.G, and Spindel, E. (1981). Immunohistochemical support for three putative transmitters on one neuron: Coexistence of 5-hydroxytrypt-amine, substance P-and thyrotropin releasing hormone-like immunoreactivity in medullary neurons projecting to the spinal cord. Neuroscience, 6, 1857–81.CrossRefPubMedGoogle Scholar
  31. Kitayama, I., Jansson, A.M., Fuxe, K., Agnati, L.F., Cintra, A., Ögren, S.-O., Härfstrand, A., Eneroth, P., Tsutsumi, T., Jonsson, G., Steinbusch, H.W.M., and Visser, T.J. (1987a). Effects of acute and chronic treatment with imipramine on 5-hydroxytrypt-amine nerve cell groups and on bulbospinal 5-hydroxytryptamine/substance P/thyro-tropin releasing hormone immunoreactive neurons in the rat. A morphometric and microdensitometric analysis. J. Neural Transm.Google Scholar
  32. Kitayama, I., Jansson, A.M., Cintra, A., Fuxe, K., Agnati, L.F., Ögren, S.-O., Härfstrand, A., Eneroth, P., and Gustafsson, J.-Å. (1987b). Effects of chronic imipramine treatment on glucocorticoid receptor immunoreactivity in various regions of the rat brain. Evidence for selective increases of glucocorticoid receptor immunoreactivity in the locus coeruleus and in the nucleus raphe magnus. J. Neural. Transm.Google Scholar
  33. Langer, S.Z., and Briley, M. (1981). High affinity 3H-imipramine binding: A new biological tool for studies in depression. Trends Neurosci., 4, 28–31.CrossRefGoogle Scholar
  34. Langer, S.Z., and Galzin, A.-M. (1987). In Fuxe, K., and Agnati, L.F. (eds.), Receptor-receptor interactions: a new intramembrane integrative mechanism, Macmillan, Basingstoke, in press.Google Scholar
  35. Mayer, G.S., and Shoup, R.E. (1983). Simultaneous multiple electrode liquid chromato-graphic-electrochemical assay for catecholamines, indolamines and metabolites on brain tissues. J. Chromatography, 255, 533–44.CrossRefGoogle Scholar
  36. Mobley, P.L., and Sulser, F. (1980a). Adrenal corticoids regulate sensitivity of noradrena-line receptor coupled adenylate cyclase in brain. Nature, 286, 608–9.CrossRefPubMedGoogle Scholar
  37. Mobley, P.L., and Sulser, F. (1980b). Adrenal steroids affect the norepinephrine sensitive adenylate cyclase system in rat limbic forebrain. Eur, J.Pharmacol., 65, 321–3.CrossRefGoogle Scholar
  38. Nilsen, O.G., Toftg, R., and Eneroth, P. (1980). Effects of acrylnitrile on rat liver cyto-chrome P-450, benzo(a)-pyrene metabolism and serum hormone levels. Tox. Lett., 6, 399–404.CrossRefGoogle Scholar
  39. Okret, S., Wikström, A.-C, Wränge, Ö., Andersson, B., and Gustafsson, J.-A. (1984). Monoclonal antibodies against the rat liver glucocorticoid receptor. Proc. Natl. Acad. Sci., 81, 1609–13.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Olson, L., and Fuxe, K. (1971). On the projections from the locus coeruleus noradrenaline neurons: the cerebellar innervation. Brain Res., 28, 165–71.CrossRefPubMedGoogle Scholar
  41. Schnapp, B.J., and Reese, T.S. (1986). New developments in understanding rapid axonal transport. Trends Neurosci., 9, 155–62.CrossRefGoogle Scholar
  42. Sheard, M.H., Zolovick, A., and Aghajanian, G.K. (1972). Effect of tricyclic antidepressant drugs. Brain Res., 43, 690–94.CrossRefPubMedGoogle Scholar
  43. Steinbusch, H.W.M., Verhofstad, A.A.J., and Joosten, H.W.J. (1978). Localization of serotonin in the central nervous system by immunohistochemistry. Neuroscience, 3, 811–19.CrossRefPubMedGoogle Scholar
  44. Sterio, D.C. (1984). The unbiased estimation of number and sizes of arbitrary particles using the disector. J. Microsc., 134, 127–36.CrossRefPubMedGoogle Scholar
  45. Sulser, F. (1984). In Advances in Biochemical Psychopharmacology, vol. 39, Raven, New York, 249–61.Google Scholar
  46. Svensson, T.H. (1978). Attenuated feed-back inhibition of brain serotonin synthesis following chronic administration of imipramine. Naunyn Schmiedeberg’s Arch. Pharmacol., 302, 115–18.CrossRefGoogle Scholar
  47. Ungerstedt, U. (1971). Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol. Scand., 367, 1–48.CrossRefGoogle Scholar
  48. Visser, T.J., and Klootwijk, V. (1981). Approaches to a markedly increased sensitivity of the radioimmunoassay for the thyrotropin-releasing hormone by derivatization. Biochem. Biophys. Acta, 673, 454–66.CrossRefPubMedGoogle Scholar
  49. Zoli, M., Agnati, L.F., Fuxe, K., Zini, I., Merlo Pick, E., Grimaldi, R., Härfstrand, A., Wikström, A.C, and Gustafsson, J.-A. (1987). Morphometrical and microdensito-metrical studies on phenylethanolamine-N-methyltransferase and neuropeptide γ-immunoreactive nerve terminals and on glucocorticoid receptor immunoreactive nerve cell nuclei in the paraventricular hypothalamic nucleus in adult and old male rats. Neuroscience, submitted.Google Scholar

Copyright information

© The Editors and the Contributors 1988

Authors and Affiliations

  • K. Fuxe
  • I. Kitayama
  • A. M. Janson
  • L. F. Agnati
  • A. Cintra
  • S. O. Ögren
  • A. Härfstrand
  • P. Eneroth
  • J.-Å Gustafsson

There are no affiliations available

Personalised recommendations