Skip to main content
SpringerLink
Log in

Estimation of the rate of 5-HT synthesis in the mouse brain by varius methods

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Non-isotopic and isotopic methods were used to estimate the rate of 5-HT synthesis in the mouse brain. 5-HT and 5_HIAA levels were measured in tissues up to 10 min after the i. p. injection of pargyline (75 or 150 mg/kg) or pheniprazine (5 or 10 mg/kg) (5-HT and 5-HIAA, MAO-inhibitor methods). 5-HIAA levels were also estimated at various times after probenecid administration (200 or 400 mg/kg i. p.) (5-HIAA-probenecid method). 5-HTP levels were estimated at various times after the blockade of 5-HTP decarboxylase by Ro4-4602. (800, 1000 or 1200 mg/kg i. p.) (5-HTP method). Finally the rate of conversion of tryptophan into 5-HT has been estimated by measuring the initial accumulation of 3H-5-HT and 3H-5-HIAA in tissues following the intravenous injection of 3H-tryptophan (isotopic method). Rates of 5-HT synthesis obtained with the two MAO inhibitor methods were much higher (about 3 to 4 times) than those calculated with the 5-HTP and 5-HIAA-probenecid methods. An intermediate rate of 5-HT synthesis was found with the isotopic technique. The high rate of 5-HT synthesis observed with the 5-HT, MAO inhibitor method (about 8 nmoles/g/h) was not related to a stimulation of 5-HT synthesis. Differences seen with all methods are discussed with respect to results obtained by various groups of workers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Azmitia, E. C., McEwen, B. S.: Corticosterone regulation of tryptophan hydroxylase in mid-brain of the rat. Science 166, 1274–1276 (1969)

    Google Scholar 

  • Brodie, B. B., Spector, S., Kuntzman, R. G., Shore, P. A.: Rapid biosynthesis of brain serotonin before and after reserpine administration. Naturwissenschaften 145, 243–244 (1958)

    Google Scholar 

  • Carlsson, A., Bédard, P., Lindqvist, M., Magnusson, T.: Physiological control of 5-HT synthesis and turnover in the brain. Fifth International Congress on Pharmacology, San Francisco, California, Abstracts of Invited presentations, p. 256 (1972a)

  • Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., Atack, C. V.: Simultaneous measurement of tyrosine and tryptohan hydroxylase activities in brain in vivo, using an inhibitor of the aromatic amino-acid decarboxylase. Naunyn-Schmiedebergs Arch. Pharmacol. 275, 153–168 (1972b)

    Google Scholar 

  • Carlsson, A., Lindqvist, M.: Accumulation of 5-hydroxytryptophan in mouse brain after decarboxylase inhibition. J. Pharm. Pharmacol. 22, 726–727 (1970)

    Google Scholar 

  • Curzon, G., Green, A. R.: Rapid method for the determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in small regions of rat brain. Brit. J. Pharmacol. 39, 653–655 (1970)

    Google Scholar 

  • Curzon, G., Joseph, M. H., Knott, P. J.: Effects of immobilization and food deprivation on rat brain tryptophan metabolism. J. Neurochem. 19, 1967–1974 (1972)

    Google Scholar 

  • Denckla, W. D., Dewey, H. H.: The determination of tryptophan in plasma liver and urine. J. Lab. clin. Med. 69, 160–169 (1967)

    Google Scholar 

  • Dubnick, B., Leeson, G., Chessin, M., Scott, C. C.: Some factors influencing the rate of accumulation of serotonin in mouse brain after inhibition of monoamine oxidase. Fall Meeting of the American Society for Pharmacology and Experimental Therapeutics, Ann. Arbor, Michigan, Abstracts of Scientific papers 10 (1958)

  • Dubnick, B., Leeson, G., Phillips, G. E.: In vivo inhibition of serotonin synthesis in mouse brain by β-phenylethylhydrazine, an inhibitor of monoamine oxidase. Biochem. Pharmacol. 11, 45 (1962)

    Google Scholar 

  • Finney, D. J.: Statistical methods in biological assay, 2nd edn. London: Charles Griffin 1964

    Google Scholar 

  • Garattini, S., Valzelli, L.: Monoamines et Système Nerveux Central, Symp. Bel-Air, Genève, Ed. J. de Ajuriaguerra, 59 (1961)

  • Glowinski, J., Hamon, M., Javoy, F., Morot-Gaudry, Y.: Rapid effects of MAO inhibitors on synthesis and release of central monoamines. In: Monoamine oxidases, New Vistas, Advanc. Biochem. Psychopharmacol. 5, 423–439 (1972)

    Google Scholar 

  • Grahame-Smith, D. G.: Studies in vitro on the relationship between brain tryptophan, brain 5-HT synthesis, and hyperactivity in rats treated by a MAOI and l-tryptophan. J. Neurochem. 18, 1053–1066 (1971)

    Google Scholar 

  • Hamon, M., Bourgoin, S., Glowinski, J.: Feedback regulation of serotonin synthesis in the rat striatum. J. Neurochem. 20, 1727–1745 (1973)

    Google Scholar 

  • Hamon, M., Bourgoin, S., Jagger, J., Glowinski, J.: Effect of LSD on synthesis and release of 5-HT in rat brain slices. Brain Res. 69, 265–280 (1974)

    Google Scholar 

  • Héry, F., Rouer, E., Glowinski, J.: Daily variations of serotonin metabolism in the rat brain. Brain Res. 43, 445–465 (1972)

    Google Scholar 

  • Karobath, M.,: Serotonin synthesis with rat brain synaptosomes. Effects of serotonin and monoamine oxidase inhibitors. Biochem. Pharmacol. 21, 1253–1263 (1972)

    Google Scholar 

  • Kaufman, S.: Properties of the pterin-dependent aromatic amino-acid hydroxylases. In: Abstracts of papers from the Ciba Foundation Symposium, May 1973. London: Elsevier, Excerpta Medica and North-Holland, P. O. Box 1270, Amsterdam (1973)

    Google Scholar 

  • Knoll, J., Magyar, K.: Some puzzling pharmacological effects of monoamine oxidase inhibitors. Monoamine oxidases, New Vistas. Advanc. Biochem. Psychopharmacol. 5, 393–405 (1972)

    Google Scholar 

  • Kellog, C.: 5-HT metabolism in the brain of mice sensitive or resistent to audiogenic seizures. J. Neurobiol. 2, 209–219 (1971)

    Google Scholar 

  • Korf, J., Van Praag, H. H., Sebens, J. B.: Serum tryptophan decreased, brain tryptophan increased and brain serotonin synthesis unchanged after probenecid loading. Brain Res. 42, 239–242 (1972)

    Google Scholar 

  • Lin, R. C., Costa, E., Neff, N. H., Wang, C. T., Ngai, S. H.: In vivo measurement of 5-hydroxytryptamine turn-over rate in the rat brain from the conversion of 14C-tryptophan to 14C-5-hydroxytryptamine, J. Pharmacol. exp. Ther. 170, 232–238 (1969)

    Google Scholar 

  • Macon, J. B., Sokoloff, L., Glowinski, J.: Feedback control of rat brain 5-hydroxytryptamine synthesis. J. Neurochem. 18, 323–331 (1971)

    Google Scholar 

  • Marshall, I., Grahame-Smith, D. G.: Evidence against a role of brain 5-hydroxy-tryptamine in the development of physical dependence upon morphine in mice. J. Pharmacol. exp. Ther. 173, 634–641 (1971)

    Google Scholar 

  • Maruyama, Y., Hayashi, G., Smits, S. E., Takemori, A. E.: Studies on the relationships between 5-hydroxytryptamine turnover in brain, and tolerance and physical dependence in mice. J. Pharmacol. exp. Ther. 178, 20–29 (1971)

    Google Scholar 

  • Meek, J., Werdinius, B.: 5-hydroxytryptamine turnover decreased by the antidepressant drug chlorimipramine. J. Pharm. Pharmacol., 22, 141–142 (1970)

    Google Scholar 

  • Millard, S. A., Gal, E. M.: The contribution of 5-hydroxyindole pyruvic acid to cerebral 5-hydroxyindole metabolism. Int. J. Neurosci. 1, 211–218 (1971)

    Google Scholar 

  • Neff, N. H., Tozer, T. N.: In vivo measurement of brain serotonin turnover. Advanc. Pharmacol. 6 A, 97–109 (1968)

    Google Scholar 

  • Neff, N. H., Tozer, T. N., Brodie, B. B.: Application of steady state kinetics to studies of the transfer of 5-HIAA from brain to plasma. J. Pharmacol. exp. Ther. 158, 214–218 (1967)

    Google Scholar 

  • Rosecrans, J. A.: Differences in brain area 5-hydroxytryptamine turnover and rearing behaviour in rats and mice of both sexes Europ. J. Pharmacol. 9, 379–382 (1970)

    Google Scholar 

  • Schechter, P. J., Lovenberg, W., Sjoerdsma, A.: Dissociation of morphine tolerance and dependence from brain serotonin synthesis rate in mice. Biochem. Pharmacol. 21, 751–753 (1972)

    Google Scholar 

  • Schubert, J.: A method for the determination of labelled 5-HT and 5-HIAA formed in vivo from 3H-tryptophan in mouse and rat brain. In: Abstract of volunteers papers of Fifth International Congress on Pharmacology, July 1972, San Francisco p. 205

  • Sharman, D. F.: Turnover of amines using probenecid to block regress of metabolites, in: Metabolism of amines in the brain, ed. by G. Hooper, Proceedings of a Symposium British and Scandinavian Pharmacological Societies, Edinburgh 1968, 34–37

  • Sheard, M. H., Aghajanian, G. K.: Neuronally activated metabolism of brain 5-HT effect of lithium. Life Sci. 9 part I, 285–290 (1970)

    Google Scholar 

  • Shen, F. H., Loh, H. H., Way, E. L.: Brain serotonin turn-over in morphine tolerant and dependent mice. J. Pharmacol. exp. Ther. 175, 427–434 (1970)

    Google Scholar 

  • Shields, P. J., Eccleston, D.: Effects of electrical stimulation of rat midbrain on 5-hydroxytryptamine synthesis as determined by a sensitive radioisotope method. J. Neurochem. 19, 265–272 (1972)

    Google Scholar 

  • Snedecor, T. W., Cochran, W. G.: Statistical methods, Iowa State University Press, Ames 1972

    Google Scholar 

  • Tagliamonte, A., Tagliamonte, P., Perez-Cruet, J., Stern, S., Gessa, G. L.: Effects of psychotropic drugs on tryptophan concentrations in the rat brain. J. Pharmacol. exp. Ther. 177, 475–480 (1971)

    Google Scholar 

  • Tozer, T. N., Neff, N. H., Brodie, B. B.: Application of steady state kinetics to the synthesis rate and turn-over time of serotonin in the brain of normal and reserpine treated rats. J. Pharmacol. exp. Ther. 153, 177–182 (1966)

    Google Scholar 

  • Tyce, G. M., Flock, E. V., Taylor, W. F., Owen, C. A. J.: Effect of ethanol on 5-hydroxytryptamine turnover in rat brain. Proc. Soc. exp. Biol. (N. Y.) 134, 40–44 (1970)

    Google Scholar 

  • Udenfriend, S., Weissbach, H.: Turnover of 5-hydroxytryptamine (Serotonin) in tissues, Proc. Soc. exp. Biol. (N.Y.) 97, 748–751 (1958)

    Google Scholar 

  • Valzelli, L., Garattini, S.: Behavioral changes and 5-hydroxytryptamine turnover in animals, Advanc. Pharmacol. 6 B, 249–259 (1968)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Groupe NB (INSERM U 114) Laboratoire de Biologie Moléculaire, Collège de France, Paris

    Y. Morot-Gaudry, M. Hamon, S. Bourgoin, J. P. Ley & J. Glowinski

  2. “Laboratoire de Biometrie”, CNRZ-INRA, Domaine de Vilvert, 78, Jouy-en-Josas

    J. P. Ley

Authors
  1. Y. Morot-Gaudry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Hamon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Bourgoin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. P. Ley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Glowinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Research Fellow from the “Laboratoire de Physiologie Acoustique” CNRZ-INRA, Domaine de Vilvert, 78 Jouy-en-Josas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morot-Gaudry, Y., Hamon, M., Bourgoin, S. et al. Estimation of the rate of 5-HT synthesis in the mouse brain by varius methods. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 223–238 (1974). https://doi.org/10.1007/BF00501231

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00501231

Key words

Search

Navigation