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Melatonin Effects on Serotonin Synthesis and Metabolism in the Striatum, Nucleus Accumbens, and Dorsal and Median Raphe Nuclei of Rats

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Abstract

This work examined the influence of the pineal gland and its hormone melatonin on the metabolism of serotonin (5-HT) in discrete areas of the forebrain, such as the Striatum and the nucleus accumbens, and the midbrain raphe. The content of 5-HT and its major oxidative metabolite, the 5-hydroxyindoleacetic acid (5-HIAA), as well as the in-vivo tryptophan hydroxylation rate were examined after long-term pinealectomy (one month) and daily melatonin treatment (500 μg/kg; twice daily for ten days) in pinealectomized rats. Pinealectomy did not alter 5-HT content in any of these brain areas, but it significantly increased the content of 5-HIAA in Striatum and the 5-HIAA/5-HT ratio in nucleus accumbens. The normal values of these parameters were recuperated after administration of exogenous melatonin, but it also increased the rate of tryptophan hydroxylation in both areas. In addition, melatonin treatment decreased the levels of 5-HIAA in dorsal raphe nucleus. These data suggest that the pineal gland, through the secretion of melatonin, modulates the local metabolism of 5-HT in forebrain areas by acting on the oxidative deamination. Moreover, melatonin injected in pinealectomized rats derives in a more extended effect than pinealectomy and induces a stimulation of 5-HT synthesis in the striatum, probably due to a pharmacological effect. These results point to the striatum as a target area for the interaction between pineal melatonin and the serotonergic function, and suggest a differential effect of the melatonin injected on areas containing serotonergic terminals and cell bodies, which may relevant for the mode of action of melatonin and its behavioral effects.

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REFERENCES

  1. Reiter, R. J. 1991. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine Rev. 12:151–180.

    Google Scholar 

  2. Redman, J. R., Armstrong, S. M., and Ng, K. T. 1983. Free running activity rhythms in the rat. Entrainment by melatonin. Science 219:1089–1091.

    Google Scholar 

  3. Sugden, D. 1983. Phychopharmacological effects of melatonin in mouse and rat. J. Pharmacol. Exp. Ther. 227:587–591.

    Google Scholar 

  4. Brown, G. M. 1995. Melatonin in psychiatric and sleep disorders. CNS Drugs 3:209–226.

    Google Scholar 

  5. Webb, S. M., and Puig-Domingo, M. 1995. Role of melatonin in health and disease. Clin. Endocrinol. 42:221–234.

    Google Scholar 

  6. Laudon, M., Nir, I. and Zisapel, N. 1988. Melatonin receptors in discrete brain areas of the male rat. Neuroendocrinology 48:577–583.

    Google Scholar 

  7. Cardinali, D. P., Vacas, M. I., Keller-Sarmiento, M. I., and Morguenstern, E. 1985. Melatonin action: sites and possible mechanisms in brain, Pages 277–302, in Axelrod, J., Fraschini, F., and Velo, G. P. (eds.), The Pineal Gland and its Endocrine Role, Plenum Press, New York.

    Google Scholar 

  8. Ruzsás, C., Fraschini, F., Peschke, E., Esposti, D., and Esposti, G. 1986. Brain neurotransmitters mediating neuroendocrine activity of melatonin. Pages 159–166, in Reiter, R. J., and Karasek, M. (eds.), Advances in Pineal Research, John Libbey & Co Ltd, London.

    Google Scholar 

  9. Dugovic, C., Leysen, J. E., and Wauquier, A. 1989. Melatonin modulates the sensitivity of 5-hydroxytryptamine-2 receptor-mediated sleep-wakefulness regulation in the rat. Neurosci. Lett. 104:320–325.

    Google Scholar 

  10. Eison, A. S., Freeman, R. P., Guss, V. B., Mullins, U. L., and Wright, R. N. 1995. Melatonin agonists modulate 5-HT2A receptor-mediated neurotransmission: behavioral and biochemical studies in the rat. J. Pharmacol. Exp. Ther. 273:304–308.

    Google Scholar 

  11. Gaffori, O., and Van Ree, J. M. 1985. Serotonin and antidepressant drugs antagonize melatonin-induced behavioral changes after injection into the nucleus accumbens of rats. Neuropharmacology 24:237–244.

    Google Scholar 

  12. Míguez, J. M., Martín, F. J., Míguez, I., and Aldegunde, M. 1991. Long-term pinealectomy alters hypothalamic serotonin metabolism in the rat. J. Pineal Res. 11:75–79.

    Google Scholar 

  13. Míguez, J. M., Martín, F. J., and Aldegunde, M. 1994. Effects of single and daily melatonin treatments on serotonin metabolism in rat brain regions. J. Pineal Res. 17:170–176.

    Google Scholar 

  14. Míguez, J. M., Martín, F. J., Lema, M., and Aldegunde, M. 1996. Changes in serotonin level and turnover in discrete hypothalamic nuclei after pinealectomy and melatonin administration to rats. Neurochem. Int. In press.

  15. Míguez, J. M., Martín, F. J., and Aldegunde, M. 1995. Effects of pinealectomy and melatonin treatments on serotonin uptake and release from synaptosomes of rat hypothalamic regions. Neurochem. Res. 20:1127–1132.

    Google Scholar 

  16. Jacobs, B. L., and Azmitia, E. A. 1992. Structure and function of the brain serotoninergic system. Physiol. Rev. 72:165–229.

    Google Scholar 

  17. Jones, D. L., Mogenson, G. J., and Wu, M. 1981. Injections of dopaminergic, cholinergic, serotoninergic and GABAergic drugs into the nucleus accumbens: effects on locomotor activity in the rat. Neuropharmacology 20:2–37.

    Google Scholar 

  18. Castillo-Romero, J. L., Vives-Montero, F., Reiter, R. J., and Acuña-Castroviejo, D. 1993. Pineal modulation of the rat caudate-putamen spontaneous neuronal activity: roles of melatonin and vasotocin. J. Pineal Res. 15:147–152.

    Google Scholar 

  19. Bliss, D. K., and Bates, P. L. 1973. A rapid and reliable technique for pinealectomising rats. Physiol. Behav. 11:111–112.

    Google Scholar 

  20. Palkovits, M. 1973. Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res. 59:449–450.

    Google Scholar 

  21. Brownstein, M. J., and Palkovits, M. 1984. Catecholamines, serotonin, acetylcholine, and γ-aminobutyric acid in the rat brain: biochemical studies, Pages 23–54, in Björklund, A., and Hökfelt, T. (eds.), Handbook of Chemical Neuroanatomy, Volumen 2, Classical Transmitters in the CNS, Part 1, Elsevier, Amsterdam.

    Google Scholar 

  22. Bradford, M. M. 1976. A raid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye-binding. Anal. Biochem. 72:248–254.

    Google Scholar 

  23. Houdouin, F., Cespuglio, R., Gharib, A., Sarda, N., and Jouvet, M. 1991. Detection of the release of 5-hydroxyindole compounds in the hypothalamus and n. raphe dorsalis throughout the sleep-waking cycle and during stressful situation in the rat: a polygraphic and voltammetric approach. Exp. Brain Res. 85:153–162.

    Google Scholar 

  24. Celada, P., and Artigas, F. 1993. Effects of local and systemic MAO inhibitors on extracellular brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the frontal cortex and raphe nuclei of freely moving rats. An in vivo microdialysis study. Naunyn-Schmiedeberg's Arch. Pharmacol. 347:583–590.

    Google Scholar 

  25. Nir, I., Behroozi, K., Assael, M., Ivriani, I., and Sulman, F. G. 1969. Changes in electrical activity of the brain following pinealectomy. Neuroendocrinology 4:122–127.

    Google Scholar 

  26. Boadle-Biber, M. C., Johannessen, J. N., Narasimhachari, N., and Phan, T. H. 1983. Activation of tryptophan hydroxylase by stimulation of central serotoninergic neurons. Biochem. Pharmacol. 32:185–188.

    Google Scholar 

  27. Urry, R. L., and Ellis, L. C. 1975. Monoamine oxidase activity of the hypothalamus and pituitary: alterations after pinealectomy, changes in photoperiod, or additions of melatonin in vitro. Experientia 31:891–892.

    Google Scholar 

  28. Cardinali, D. P., Nagle, C. A., Freire, F., and Rosner, J. M. 1975. Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus. Neuroendocrinology 18:72–85.

    Google Scholar 

  29. Alexiuk, N. A., and Vriend, J. 1991. Effects of daily afternoon melatonin administration on monoamine accumulation in median eminence and striatum of ovariectomized hamsters receiving pargyline. Neuroendocrinology 54:55–61.

    Google Scholar 

  30. Quay, W. B. 1989. Changes with darkness in regional brain 5-hydroxytryptamine and 5-hydroxyindole acetic acid: local differences with pinealectomy, sham surgery, and melatonin. Neurochem. Res. 14:957–961.

    Google Scholar 

  31. Felten, D. L., and Harrigan, P. 1980. Dendrite bundles in nuclei raphe dorsalis and centralis superior of the rabbit: a possible substrate for local control of serotonergic neurons. Neurosci. Lett. 16:275–280.

    Google Scholar 

  32. Pecci-Saavedra, J., Brusco, A., Peressine, S., and Oliva, D. 1986. A new case for a presynaptic role of dendrites: an immunocy-toachemical study of the N. raphé dorsalis. Neurochem. Res. 11:997–1009.

    Google Scholar 

  33. 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.

    Google Scholar 

  34. Hjorth, S., and Sharp, T. 1991. Effect of the 5-HT1A receptors agonist 8-OH-DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis. Life Sci. 48:1779–1786.

    Google Scholar 

  35. Alexander, G. E., and Crutcher, M. D. 1990. Functional architecture of basal ganglia circuits: neural sustrates of parallel processing. Trends Neurosci. 13:266–271.

    Google Scholar 

  36. Nedergaard, S., Bolam, J. P., and Grennfield, S. A. 1988. Facilitation of a dendritic calcium conductance by 5-hydroxytryptamine in the substantia nigra. Nature 333:174–177.

    Google Scholar 

  37. Parsons, L. H., and Justice, J. B. 1993. Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. Brain Res. 606:195–199.

    Google Scholar 

  38. Cross, A. J. 1988. Serotonin in neurodegenerative disorders. Pages 231–253, in Osborne, N. N., and Hamon, M. (eds.), Neuronal serotonin. Wiley. New York.

    Google Scholar 

  39. Scatton, B., Javoy-Agid, F., Montfort, J. C., and Agid, Y. 1984. Neurochemistry of monoaminergic neurons in Parkinson's disease. Pages 43–52, in Usdin, E., Carlsson, A., Dahlström, A., and Engel, J. (eds.), Catecholamines: Neuropharmacology and Central Nervous System-Therapeutic aspects. Alan L. Liss. New York.

    Google Scholar 

  40. Durlach-Nisteli, C., and Van Ree, J. M. 1992. Dopamine and melatonin in the nucleus accumbens may be implicated in the mode of action of antidepressant drugs. Eur. J. Pharmacol. 217:15–21.

    Google Scholar 

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Míguez, J.M., Martín, F.J. & Aldegunde, M. Melatonin Effects on Serotonin Synthesis and Metabolism in the Striatum, Nucleus Accumbens, and Dorsal and Median Raphe Nuclei of Rats. Neurochem Res 22, 87–92 (1997). https://doi.org/10.1023/A:1027337606929

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