Summary
Hemisection of the brains of rats was performed at a level slightly rostral to the mesencephalo-diencephalic junction. In chronic experiments (7 to 14 days after the lesion) a considerable decrease in 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels was found in the ipsilateral hemiforebrain. In acute experiments (3 to 6 h after the lesion) the effect of the lesion on synthesis and metabolism of 5-HT was investigated by estimating tryptophan, 5-hydroxytryptophan (5-HTP), 5-HT and 5-HIAA levels in different parts of the brain. In order to get an insight into the different steps in 5-HT metabolism inhibitors of enzymes or transport were used (Ro 4-4602 [N-(dl-seryl)-N1-(2,3,4-trihydroxybenzyl) hydrazine], pargyline, and probenecid). The effect of l-tryptophan loading was also investigated.
The accumulation of 5-HTP and 5-HT following inhibition of 5-HTP decarboxylase and monoamine oxidase, respectively, was not significantly influenced by the hemisection. On the other hand, the accumulation of 5-HIAA following probenecid treatment, and the disappearance of 5-HT and 5-HIAA following inhibition of 5-HTP decarboxylase and monoamine oxidase, respectively, were slightly or moderately retarded.—The tryptophan level was moderately increased on the side of the lesion.
The data indicate that a considerable synthesis and metabolism of 5-HT occurs intraneuronally even in the absence of an impulse flow. The nerve impulses induce an increased release and extraneuronal metabolism, primarily at the expense of stored 5-HT. In addition, the nerve impulses possibly cause a certain increase in 5-HT synthesis.
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References
Andén, N.-E., Carlsson, A., Hillarp, N.-Å, Magnusson, T.: 5-Hydroxytryptamine release by nerve stimulation of the spinal cord. Life Sci. 3, 473–478 (1964).
—, Dahlström, A., Fuxe, K., Larsson, K., Olson, L., Ungerstedt, U.: Ascending monoamine neurons to the telencephalon and diencephalon. Acta physiol. scand. 67, 313–326 (1966a).
—, Fuxe, K., Hökfelt, T.: The importance of nervous impulse flow for the depletion of the monoamines from central neurons by some drugs. J. Pharm. Pharmacol. 18, 630–632 (1966b).
—, Magnusson, T.: An improved method for the fluorimetric determination of 5-hydroxytryptamine in tissues. Acta physiol. scand. 69, 87–94 (1967).
Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970).
Bédard, P., Carlsson, A., Fuxe, K., Lindqvist, M.: Origin of 5-hydroxytryptophan and l-DOPA accumulating in brain following decarboxylase inhibition. Naunyn-Schmiedebergs Arch. Pharmak. 269, 1–6 (1971).
Carlsson, A., Lindqvist, M.: Accumulation of 5-hydroxytryptophan in mouse brain after decarboxylase inhibition. J. Pharm. Pharmacol. 22, 726–727 (1970).
Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine containing neurons in the central nervous system. I: Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, Suppl. 232, 1–55 (1964).
Giacalone, E., Kostowski, W.: Lesions of the midbrain raphe in the rat. Effect on level of biogenic amines in forebrain and spinal cord. Pharmacol. Res. Comm. 1, 1 (1969).
Grahame-Smith, D. G.: Studies “in vivo” on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and l-tryptophan. J. Neurochem. 18, 1053–1066 (1971).
Green, H., Sawyer, J. L.: Demonstration, characterization, and assay procedure of tryptophan hydroxylase in rat brain. Analyt. Biochem. 15, 53–64 (1966).
Heller, A., Seiden, L. S., Porcher, W., Moore, R. Y.: 5-Hydroxytryptophan decarboxylase in rat brain: Effect of hypothalamic lesions. Science 147, 887 (1965).
Korf, J., Valkenburg-Sikkema, T.: Fluorimetric determination of 5-hydroxyindoleacetic acid in human urine and cerebrospinal fluid. Clin. chim. Acta 26, 301–306 (1969).
Lindqvist, M.: Quantitative estimation of 5-hydroxy-3-indole acetic acid and 5-hydroxytryptophan in the brain following isolation by means of a strong cation exchange column. Acta pharmacol. (Kbh.) 29, 303–313 (1971).
Meek, J. L., Fuxe, K.: Serotonin accumulation after monoamine-oxidase inhibition. Biochem. Pharmacol. 20, 693–706 (1971).
Moir, A. T. B., Eccleston, D. J.: The effect of precursor loading in the cerebral metabolism of 5-hydroxyindoles. J. Neurochem. 15, 1093–1108 (1968).
Moore, R. Y., Wong, S. R., Heller, A.: Regional effects of hypothalamic lesions on brain serotonin. Arch. Neurol. (Chic.) 13, 346 (1965).
Neff, N., Tozer, T., Brodie, B. B.: Application of steady-state kinetics to studies of the transfer of 5-hydroxyindoleacetic acid from brain to plasma. J. Pharmacol. exp. Ther. 158, 214–218 (1967).
Poirier, L. J., McGeer, E. I., Larochelle, L., McGeer, P. L., Bédard, P., Boucher, R.: The effect of brain stem lesions on tyrosine and tryptophan hydroxylases in various structures of the telencephalon of the cat. Brain Res. 14, 147–155 (1969).
—, Singh, P., Boucher, R., Bouvier, G., Olivier, A., Larochelle, P.: Effect of brain lesions on striatal monoamines in the cat. Arch. Neurol. (Chic.) 17, 601–608 (1967).
—, Sourkes, T. L., Bouvier, G., Boucher, R., Carabin, S.: Striatal amines, experimental tremor and the effect of harmaline in the monkey. Brain 89, 37–52 (1966).
Sheard, M. H., Aghajanian, G. K.: Stimulation of the midbrain raphe: Effect on serotonin metabolism. J. Pharmacol. exp. Ther. 163, 425 (1968).
Tagliamonte, A., Tagliamonte, P., Perez-Cruet, J., Stern, S., Gessa, G. L.: Effect of psychotropic drugs on tryptophan concentration in the rat brain. J. Pharmacol. exp. Ther. 177, 475–480 (1971).
Weber, L. J., Horita, A.: A study of 5-hydroxytryptamine formation from l-tryptophan in the brain and other tissues. Biochem. Pharmacol. 14, 1141 (1965).
Werdinius, B.: Effect of probenecid on the levels of monoamine metabolism in the rat brain. Acta pharmacol. (Kbh.) 25, 18–23 (1967).
Winer, B. J.: Statistical principles in experimental design. New York: McGraw-Hill Book Comp. 1962.
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Bédard, P., Carlsson, A. & Lindqvist, M. Effect of a transverse cerebral hemisection on 5-hydroxytryptamine metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 1–15 (1972). https://doi.org/10.1007/BF00498790
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DOI: https://doi.org/10.1007/BF00498790