Summary
The effect of various pharmacological treatments on the levels of free and total 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain were investigated using a gas chromatographic-mass spectrometric technique. The disappearance of 5-HTOL following monoamine oxidase (MAO) inhibition induced by pargyline was more rapid (t1/2 10–15 min) than that of 5-HIAA (t1/2 30–40 min) in all regions investigated, indicating a rapid turnover of 5-HTOL. The selective MAO-A inhibitor chlorgyline produced a more pronounced reduction of 5-HTOL than of 5-HIAA, while the MAO-B inhibitor deprenyl was without effect on both serotonin metabolites. The MAO-A inhibitor amiflamine which is selective for serotonin neurons, was also more effective in reducing free 5-HTOL levels than of 5-HIAA levels, suggesting that the formation of 5-HTOL is closely associated with serotonin neurons. Neonatal treatment with the serotonin neurotoxin 5, 7-dihydroxytryptamine (5, 7-HT) led to a more pronounced reduction of 5-HTOL levels in cerebral cortex than that of 5-HIAA levels, while the increase of 5-HTOL levels in pons-medulla was more marked than of 5-HIAA levels. Probenecid treatment increased several fold both conjugated 5-HTOL and 5-HIAA levels in brain tissue. An increase was also noted for free 5-HTOL, although of less magnitude. Treatment with the serotonin receptor active agents methiothepin andd-lysergic acid diethylamide produced similar alterations of free 5-HTOL and 5-HIAA. The present results have demonstrated that free 5-HTOL has a rapid turnover in rat brain and that free 5-HTOL levels may serve as a useful index for serotonin turnover.
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References
Andén N-E, Corrodi H, Fuxe K, Hökfelt T (1986) Evidence for a central 5-hydroxytryptamine stimulation by lysergic acid diethylamide. Br J Pharmacol 34: 1–7
Ask AL, Fagervall I, Ross SB (1982) Evidence for a selective inhibition of (+)-FLA 336 of monoamine oxidase in serotonergic neurons in rat brain. Acta Pharmacol Toxicol (Copenh) 51: 395–396
Beck O, Borg S, Eriksson L, Lundman A (1982) 5-Hydroxytryptophol in the cerebrospinal fluid and urine of alcoholics and healthy subjects. Naunyn Schmiedebergs Arch Pharmacol 321: 293–297
Beck O, Borg S, Homstedt B, Stibler H (1980) Levels of 5-hydroxytryptophol in cerebrospinal fluid from alcoholics determined by gas chromatography-mass spectrometry. Biochem Pharmacol 29: 693–696
Beck O, Borg S, Jonsson G, Lundman A, Valverius P (1984) Measurement of 5-hydroxytryptophol and 5-hydroxyindoleacetic acid in human and rat brain and plasma. J Neural Transm 59: 57–67
Beck O, Sedvall G (1975) The synthesis of 5-hydroxyindole-3-(2-D2-acetic acid) andα, α′, β, β′-D4-5-hydroxytryptamine. J Lab Comp 11: 57–61
Bourgoin S, Artaud F, Enjalbert A, Hery F, Glowinski J, Hamon M (1977) Acute changes in central serotonin metabolism induced by blockade or stimulation of serotoninergic receptors during ontogenesis in the rat. J Pharmacol Exp Ther 202: 519–531
Bosin T (1978) Serotonin metabolism. In: Essman WB (ed) Serotonin in health and disease, vol 1. Spectrum Publ, New York, pp 181–300
Cerrito F, Raiteri M (1979) Serotonin release is modulated by presynaptic autoreceptors. Eur J Pharmacol 57: 427–430
Cheifetz S, Warsh JJ (1980) Occurrence and distribution of 5-hydroxytryptophol in the rat. J Neurochem 34: 1093–1099
Curtius HC, Wolfensberger M, Redweik U, Leimbacher W, Maibach RA, Ister W (1975) Mass fragmentography of 5-hydroxytryptophol and 5-methoxytryptophol in human cerebrospinal fluid. J Chromatogr 112: 523–531
Diggory GL, Ceasar PM, Hazelby D, Taylor KT (1979) Endogenous 5-hydroxytryptophol in mouse brain. J Neurochem 32: 1323–1325
Finberg JPM, Youdim MBH (1983) Selective MAO-A and B inhibitors: their mechanism of action and pharmacology. Neuropharmacol 22: 441–446
Fuller RW (1980) Pharmacology of central serotonin neurons. Ann Rev Toxicol 20: 111–127
Hesselgren T, Beck O (1980) Synthesis of six specifically deuterated indoles of biological interest. J Lab Cop Radiopharmac 17: 411–419
Jonsson G, Hallman H, Sundström E (1982) Effects of the noradrenaline neurotoxin DSP 4 on the postnatal development of central noradrenaline neurons in the rat. Neurosci 7: 2895–2907
Jonsson G, Pollare T, Hallman H, Sachs Ch (1978) Developmental plasticity of central serotonin neurons after 5, 7-dihydroxytryptamine treatment. Ann NY Acad Sci 305: 328–345
Korf J, Van Praag HM, Sebens JB (1972) Serum tryptophan decreased, brain tryptophan increased and brain serotonin synthesis unchanged after tryptophan loading. Brain Res 42: 239–242
Kveder S, Iskric S, Kelevic D (1962) 5-Hydroxytryptophol: a metabolite of 5-hydroxytryptamine in rats. Biochem J 85: 447–449
Monachon M-A, Burkard WP, Jalfre M, Haefely W (1972) Blockade of central 5-hydroxytryptamine receptors by methiothepin. Naunyn Schmiedebergs Arch Pharmacol 274: 192–197
Ponzio F, Jonsson G (1979 a) Effects of neonatal 5, 7-dihydroxytryptamine treatment on the development of serotonin neurons and their transmitter metabolism. Dev Neurosci 1: 80–89
Ponzio F, Jonsson G (1979 b) A rapid and simple method for the determination of picogram levels of serotonin in brain tissue using liquid chromatography with electrochemical detection. J Neurochem 32: 129–132
Takahashi S, Godse DD, Naqvi A, Warsh JJ, Stancer HC (1978) 5-Hydroxytryptophol in human cerebrospinal fluid: quantitative determination by gas chromatography-mass spectrometry using a deuterated internal standard. Clin Chim Acta 84: 55–62
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Beck, O., Lundman, A. & Jonsson, G. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid levels in rat brain: Effects of various drugs affecting serotonergic transmitter mechanisms. J. Neural Transmission 69, 287–298 (1987). https://doi.org/10.1007/BF01244349
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DOI: https://doi.org/10.1007/BF01244349