Serotonin pp 67-79 | Cite as

Anatomical Evidence for GABA-5 HT Interaction in Serotonergic Neurons

  • Jean-François Pujol
  • Marie-Françoise Belin
  • Halima Gamrani
  • Michèle Aguera
  • André Calas
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 133)


Numerous studies have indicated possible metabolic interactions between GABA and monoamines 1,2,3,4,5,6,7,8. Recently, it was postulated that GABA could be responsible for inhibition of the firing of serotonin (5 HT) containing neurons of the nucleus raphe dorsalis (NRD) 9,10,11,12. Recently 13,14,15 we have demons-trated the presence of terminals, fibers and nerve cell bodies accumulating 3H GABA in the NRD. These elements were postulated to belong to a local GABAergic network since lesions of principal NRD afferents failed to produce important changes in glutamate decarboxylase (GAD) activity. Finally, such elements were observed in all the periventricular area and could correspond to the existence of a periventricular GABAergic system.


Nucleus Raphe Dorsalis Serotonergic Neuron Glutamate Decarboxylase Neuronal Uptake Clear Vesicle 
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  1. 1.
    W.J. Nickles, S. Berl and D.D. Clarke, Interaction of catecholamine and amino acid metabolism in brain: effect of pargyline and L-DOPA, J. Neurochem. 23: 149 (1974).CrossRefGoogle Scholar
  2. 2.
    C.J. Patel, R.P. Schatz, S.M. Constantinides and L.A.L. Harbans, Effects of desipramine and pargyline on brain gamma-aminobutyric acid, Biochem. Pharmacol. 24: 57 (1975).Google Scholar
  3. 3.
    N.H. Yessaian, A.H. Demirjian and B.V. Tozakalian, Effect of GABA, picrotoxin and bicuculline on loss of noradrenaline and serotonin from rat brain mesodiencephalic region in vitro, Biochem. Pharmacol. 28: 1151 (1976).Google Scholar
  4. 4.
    N.H. Yessaian, A.R. Armenian, E.K. Kazarova and H.Ch. Buniatian, On the involvement of inorganic ions in the effect of y-aminobutyric acid on brain serotonin and norepinephrine, J. Neurochem. 19: 307 (1971).CrossRefGoogle Scholar
  5. 5.
    N.E. Anden and G. Stock, Inhibitory effec of hydroxybutyric acid and aminobutyric acid on the dopamine cells in the substantia nigra, Naunyn-Schmiedeberg’s Arch. Exp. Path. Pharmak. 279: 89 (1973).Google Scholar
  6. 6.
    G. Bartholini and H. Stadler, Cholinergic and GABAergic influences on the dopamine release in extrapyramidal centers, in: “Chemical tools in catecholamine research” vol II, S. Almgren, A. Carlsson and J. Engel, ed., North-Holland Publishing Co, Amsterdam (1975).Google Scholar
  7. 7.
    A. Cheramy, A. Nieoullon and J. Glowinski, GABAergic processes involved in the control of dopamine release from nigrostriatal dopaminergic neuorns in the cat, Europ. J. Pharmacol. 48: 281 (1978).Google Scholar
  8. 8.
    P.M. Groves, C.J. Wilson, S.J. Young and G.V. Rebec, Self inhibition by dopaminergic neurons, Science 190: 522 (1975).PubMedCrossRefGoogle Scholar
  9. 9.
    D.W. Gallager and G.K. Aghajanian, Effect of antipsychotic drugs on the firing of drosal raphe cells. I - Role of adrenergic system, Europ. J. Pharmacol. 39: 341 (1976).Google Scholar
  10. 10.
    D.W. Gallager and G.K. Aghajanian, Effect of antipsychotic drugs on the firing of dorsal raphe cells. II - Reversal by picrotoxin, Europ. J. Pharmacol. 39: 357 (1976).Google Scholar
  11. 11.
    R.Y. Wang, Physiological evidence for habenula as major link between forebrain and midbrain raphe, Science 197: 89 (1977).PubMedCrossRefGoogle Scholar
  12. 12.
    R.Y. Wang, D.W. Gallager and G.W. Aghajanian, Stimulation of pontine reticular formation supresses firing of serotonergic neurones in the dorsal raphe, Nature 264: 365 (1976).PubMedCrossRefGoogle Scholar
  13. 13.
    M.F. Belin, M. Aguera, M. Tappaz and J.F. Pujol, Identification of GABA accumulating neurons in the nucleus raphe dorsalis, C.R. Acad. Sci. 287: 865 (1978).Google Scholar
  14. 14.
    M.F. Belin, A. Aguera, M. Tappaz, A. McRae-Degueurce,P. Bobillier and J.F. Pujol, GABA-accumulating neurons in the nucleus raphe dorsalis and periaqueductal gray in the rat: a biochemical and radioautographic study, Brain Res. 170: 279 (1979).PubMedCrossRefGoogle Scholar
  15. 15.
    H. Gamrani, A. Calas, M.F. Belin, M. Aguera and J.F. Pujol, High resolution radioautographic identification of 3H GABA labeled neurons in the rat raphe dorsalis, Neurosci. Let., in press.Google Scholar
  16. 16.
    M.W. Brightman and S.L. Palay, The fine structure of ependyma in the brain of the rat, J. Cell. Biol. 19: 415 (1963).PubMedCrossRefGoogle Scholar
  17. 17.
    E. Westergaard, The fine structure of nerve fibers and endings in the lateral cerebral ventricles of the rat, J. Comp. Neurol. 144: 345 (1972).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Calas, 0. Bosler, M. Arluison and C. Bouchaud, Serotonin as a neurohormone in circumventricular organs and subependymal fibers, in: “Brain endocrine interaction. III - Neural hormones and reproduction, D.E. Scott, G.P. Kozlowski and A. Weindl, ed., S. Karger, Basel (1978).Google Scholar
  19. 19.
    G. Richards, H.P. Lorez and J.P. Tranzer, Indolealkylamine nerve terminals in cerebral ventricles: identification by electron microscopy and fluorescence histochemistry, Brain Res. 57: 277 (1973).PubMedCrossRefGoogle Scholar
  20. 20.
    G. Alonso, E Pons et J. Cadilhac, Mise en évidence par radio-autographie de terminaisons indolaminergiques dans les parois ventriculaires cérébrales chez le rat, C.R. Soc. Biol. 168: 1021 (1974).Google Scholar
  21. 21.
    H.P. Lorez and J.G. Richards, 5 HT nerve terminals in the fourth ventricle of the rat brain: their identification and distribution studied by fluorescence,histochemistry and electron microscopy, Cell. Tiss. Res. 165: 37 (1975).Google Scholar
  22. 22.
    J.G. Richards, Autoradiographic evidence for the selective accumulation of 3H 5 HT by supra-ependymal nerve terminals, Brain Res. 134: 151 (1977).PubMedCrossRefGoogle Scholar
  23. 23.
    V. Chan-Palay, Serotonin axons in the supra-and sub-ependymal plexuses and in the leptomeninges; their roles in local alterations of cerebrospinal fluid and vasomotor activity, Brain Res. 102: 103 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    L. Descarries, A. Beaudet and K.C. Watkins, Serotonin nerve terminals in adult rat neoccrtex, Brain Res. 100: 563 (1975).PubMedCrossRefGoogle Scholar
  25. 25.
    F. Larra et B. Droz, Techniques radioautographiques et leur application à l’étude du renouvellement des constituants cellulaires, J. Microscopie 9: 845 (1970).Google Scholar
  26. 26.
    M.F. Belin, H. Gamrani, M. Aguera, A. Calas and J.F. Pujol, Selective uptake of GABA by rat supra and sub-ependymal nerve fibers. Histological and high resolution radioautographic studies, submitted to Neuroscience.Google Scholar
  27. 27.
    D.L. Martin and A.A. Smith, Ions and the transport of GABA by synaptosomes, J. Neurochem. 19: 841 (1972).PubMedCrossRefGoogle Scholar
  28. 28.
    G. Levi and M. Raiteri, Exchange of neurotransmitter amino-acid at nerve endings can simulate high affinity uptake, Nature 250: 735 (1974).PubMedCrossRefGoogle Scholar
  29. 29.
    F. Gonon, Mesure en continu du transport actif par les synaptosomes: application à l’étude du transport d’un neurotransmetteur (GABA), Thèse présentée à l’Université Claude Bernard, Lyon I (1979).Google Scholar
  30. 30.
    N. Halasz, A. Ljungdahl and T. Hokfelt, Transmitter histochemistry of the rat olfactory bulb. III - Autoradiographic localisation of 3H GABA, Brain Res. 167: 221 (1979).PubMedCrossRefGoogle Scholar
  31. 31.
    V. Chan-Palay, Autoradiography localisation of y-aminobutyric acid receptors in the rat central nervous system using 3H muscimol, Proc. Nat. Acad. Sci. (U.S.A.) 75: 1024 (1978).CrossRefGoogle Scholar
  32. 32.
    N.G. Bowery, G.P. Jones and M.J. Neal, Selective inhibition of neuronal GABA uptake by Cis-1,3-aminocyclohexane carboxylic acid, Nature 264: 281 (1976).CrossRefGoogle Scholar
  33. 33.
    J.S. Kelly and P. Dick, Differential labelling of glial cells and GABA-inhibitory interneurons and nerve terminals following the microinjection of 3H $Alanine, 3H DABA and 3H GABA into single folia of the cerebellum, in “Cold Spring Habor Symposia on quantitative biology, vol 10 The synapse (1976).Google Scholar
  34. 34.
    W. Noack, L. Dumitrescu and J.U. Schweichel, Scanning and electron microscopical investigations of the surface structures of the lateral ventricles in the cat, Brain Res. 46: 121 (1972).PubMedCrossRefGoogle Scholar
  35. 35.
    J.E. Bruni, D.G. Montemurro, R.E. Clattenburg and R.P. Singh, Scanning electron microscopy of the ependymal surface of the third ventricle after silver nitrate staining, Brain Res. 61: 207 (1973).PubMedCrossRefGoogle Scholar
  36. 36.
    W.K. Paull, H. Martin and D.E. Scott, Scanning electron microscopy of the third ventricular floor of the rat, J. Comp. Neurol. 175: 301 (1974).CrossRefGoogle Scholar
  37. 37.
    R. Bleier, Surface fine structure of supra-ependymal elements and ependyma of hypothalamic third ventricle of mouse, J. Comp. Neurol. 161: 555 (1975).PubMedCrossRefGoogle Scholar
  38. 38.
    A. Mitro, Light microscopy and histochemical study of the ependyma of the third cerebral ventricle in the albino rat, Folia Morphol. 23: 347 (1975).Google Scholar
  39. 39.
    A. Nitro and A. Kiss, The ependyma of the ventriculus mesencephali in the rat, Acta Morphol. Acad. Sci. Hung. 25: 1 (1977).Google Scholar
  40. 40.
    R.N.J. Cupedo, The surface ultrastructure of the habenular complex of the rat, Anat. Embryol. 152: 43 (1977).CrossRefGoogle Scholar
  41. 41.
    T. Yamamori, The directions of ciliary beat on the wall of the fourth ventricle in the mouse, Arch. Histol. Jap. 40: 283 (1977).CrossRefGoogle Scholar
  42. 42.
    A. Kiss and A. Mitro, Ependyma and supraependymal structures in some areas of the fourth ventricle in the rat, Acta Anat. 100: 521 (1978).PubMedCrossRefGoogle Scholar
  43. 43.
    G.K. Aghajanian and D.W. Gallager, Raphe origin of serotonergic nerves terminating in the cerebral ventricles, Brain Res. 88: 221 (1975).PubMedCrossRefGoogle Scholar
  44. 44.
    H.P. Lorez, L. Pieri and J.G. Richards, Disappearance of supraependymal 5 HT axons in the rat forebrain after electrolytic and 5,6-DHT-induced lesions of the medial forebrain bundle, Brain Res. 100: 1 (1975).PubMedCrossRefGoogle Scholar
  45. 45.
    H.P. Lorez and J.G. Richards, Effects of intra cerebroventricular injection of 5,6-dihydroxytryptamine and 6-hydroxydopamine on supra-ependymal nerves, Brain Res. 116: 165 (1976).PubMedCrossRefGoogle Scholar
  46. 46.
    V. Chan-Palay, Indoleamine neurons and their processes in’the normal rat brain and in chronic diet-induced thiamine deficiency demonstrated by uptake of 3H-serotonin, J. Comp. Neurol. 176: 467 (1977).PubMedCrossRefGoogle Scholar
  47. 47.
    L.L. Iversen and F.E. Bloom, Studies if the uptake of 3H GABA and 3H glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography, Brain Res. 41: 131 (1972).PubMedCrossRefGoogle Scholar
  48. 48.
    T. Hattori, P.L. McGeer, H.C. Fibiger and E.G. McGeer, On the source of GABA-containing terminals in the substantia nigra. Electron microscopic autoradiographic and biochemical studies, Brain Res. 54: 103 (1973).PubMedCrossRefGoogle Scholar
  49. 49.
    C. Sotelo, Radioautography as a tool for the study of putative neurotransmitters in the nervous system, J. Neur. Trans. suppl. XII: 75 (1975).Google Scholar
  50. 50.
    T. Hökfelt and A Ljungdhal, Autoradiographic identification of cerebral and cerebellar cortical neurones accumulating labelled gamma-aminobutyric acid (3H GABA), Exp. Brain Res. 14: 354 (1972).PubMedCrossRefGoogle Scholar
  51. 51.
    R.W. Burry and R.S. Lasher, Electron microscopic autoradiography of the uptake of (3H) GABA in dispersed cell cultures of rat cerebellum. I - The morphology of the GABAergic synapse, Brain Res. 151: 1 (1978).PubMedCrossRefGoogle Scholar
  52. 52.
    J.S. Kim, I.J. Bak, R. Hassler and Y. Okada, Role of y-aminobutyric acid (GABA) in the extra-pyramidal motor system. 2. Some evidence for the existence of a type of GABA-rich strionigral neurons, Exp. Brain Res. 14: 95 (1971).PubMedCrossRefGoogle Scholar
  53. 53.
    J. Storm-Mathisen, GABA as a transmitter in the central nervous system of vertebrates, J. Neur. Trans. Suppl. XI: 227 (1974).Google Scholar
  54. 54.
    F. Schon and L.L. Iversen, The use of autoradiographic techniques for the identification and mapping of transmitter-specific neurones in the brain, Life Sci. 15: 157 (1974).PubMedCrossRefGoogle Scholar
  55. 55.
    B.J. McLaughlin, J.G. Wood, K. Saito, R. Barber, J.E. Baughn, E. Roberts and J.Y. Wu, The fine structural localisation of glutamate decarboxylase in synaptic terminals of rodent cerebellum, Brain Res. 76: 377 (1974).PubMedCrossRefGoogle Scholar
  56. 56.
    J. Storm-Mathisen, High affinity uptake of GABA in presumed GABAergic nerve endings in rat brain, Brain Res. 84: 409 (1975).PubMedCrossRefGoogle Scholar
  57. 57.
    C.E. Ribak, J.E. Vaughn, K. Saito, R. Barber and E. Roberts, Immunocytochemical localization of glutamate decarboxylase in rats substantia nigra, Brain Res. 116: 287 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Jean-François Pujol
    • 1
    • 2
  • Marie-Françoise Belin
    • 1
    • 2
  • Halima Gamrani
    • 1
    • 2
  • Michèle Aguera
    • 1
    • 2
  • André Calas
    • 1
    • 2
  1. 1.INSERM U 171LyonFrance
  2. 2.CNRS, INP 08MarseilleFrance

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