Abstract
The relationships between tryptophan (Trp) and its major CNS metabolites serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) may be studied by analysis of post-mortem tissue or by analyzing concentrations in the extracellular fluid. Major advances in our understanding of the physiological importance of Trp supply to the brain and subsequent 5-HT synthesis and metabolism was derived, in part, from regional brain tissue analysis following e.g. Trp loading, stress, fasting (Fernstrom and Wurtman, 1971; Knott and Curzon, 1974; Curzon and Marsden, 1975). However, tissue analysis does not differentiate between functionally active substrate concentrations available to receptors in the extracellular compartment and intracellular concentrations. Furthermore, as only a single value is obtained from each animal, large numbers of animals are required to obtain temporal profiles of drug action. The primary advantage of in vivo monitoring of extracellular substrate concentrations is that repeated measurements may be made in the same animal over time. When applied to the conscious, freely moving animal, this allows associations between neurochemical changes and their roles in behaviors to be determined.
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References
Adell, A., Sarna, G.S., Hutson, P.H., and Curzon, G., 1989, An in vivo dialysis and behavioral study of the release of 5-HT by p-chloro-amphetamine in reserpinized rats, Brit. J. Pharmacol., 97: 206–212.
Alexander, G.M., Grothusen, J.R., and Schwartzman, R.J., 1988, Flow dependent changes in the effective surface area of microdialysis probes, Life Sci., 43: 595–601.
Anderson, G.M., Teff, K.L., and Young, S.N., 1987, Serotonin in cisternal cerebrospinal fluid of the rat: measurement and use as an index of functionally active serotonin, Life Sci., 40: 2253–2260.
Auerbach, S., and Lipton, P., 1985, Regulation of serotonin release from the in vitro rat hippocampus: effects of alterations in levels of depolarization and rates of serotonin metabolism, J. Neurochem., 44: 1116–1130.
Azmitia, E.C., and Segal, M., 1978, An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat, J. Comp. Neurol., 179: 641–669.
Baumann, P.A., and Waldmeier, P.C., 1984, Negative feedback control of serotonin release in vivo: comparison of 5-hydroxy-indoleacetic acid levels measured by voltammetry in conscious rats and by biochemical techniques, Neuroscience, 11: 195–204.
Benveniste, H., and Diemer, N.H., 1987, Cellular reactions to implantation of a microdialysis tube in the rat hippocampus, Acta Neuropathol., 74: 234–238.
Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N.H., 1984, Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral dialysis, J. Neurochem., 43: 1369–1374.
Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N.H., 1987, Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat, J. Neurochem., 49: 729–734.
Bito, L., Davson, H., Levin, E., Murray, M., and Sider, N., 1966, The concentrations of free amino acids and other electrolytes in cerebrospinal fluid, in vivo dialysate of brain, and blood plasma of the dog, J. Neurochem., 13: 1057–1067.
Blundell, J.E., 1984, Serotonin and appetite, Neuropharmacology, 23: 1537–1551.
Bonanno, G., Maura, G., and Raiteri, M., 1986, Pharmacological characterization of release regulating serotonin autoreceptors in rat cerebellum, Eur. J. Pharmacol., 126: 317.
Burns, D., London, J., Brunswick, D.J., Pring, M., Garfinkel, D., Rabinowitz, J.L., and Mendels, J., 1976, A kinetic analysis of 5-hydroxyindoleacetic acid excretion from rat brain and CSF, Biol. Psych., 11: 125–157.
Chan-Palay, V., 1976, Serotonin afferents from raphe nuclei to the cerebellum in mammals, Exp. Brain Res., Suppl., 1: 20–25.
Church, W.H., and Justice, J.B., 1986, Sampling considerations for on-line microbore liquid chromatography of brain dialysate, 58: 1649–1656.
Commissiong, J.W., 1985, Monoamine metabolites: their relationship and lack of relationship to monoaminergic neuronal activity, Biochem. Pharmacol., 34: 289–290.
Cudennec, A., Duverger, D., Serrano, A., Scatton, B., and Mackenzie, E.T., 1988, Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. II. Effects of electrical stimulation of the rostral raphe nuclei, Brain Res., 444: 227–246.
Curzon, G., 1986, Critique: serotonin neurochemistry revisited: a new look at some old axioms, Neurochem. Int., 2: 155–159.
Curzon, G., and Marsden, C.A., 1975, Metabolism of a tryptophan load in the hypothalamus and other brain regions, J. Neurochem., 25: 251–256.
Defeudis, F.V., 1986, New studies on cerebrovascular endothelium — possible reference to the interpretation of ‘precursor-loading’ experiments, Trends Pharmacol. Sci., 7: 51–52.
Delgado, J.M.R., Defeudis, F.V., Roth, R.H., Ryugo, D.K., and Mitruka, B.M., 1972, Dialtrode for long term intracerebral perfusion in the awake cat brain, J. Arch. Int. Pharmacodyn., 198: 9–21.
De Simoni, M.G., Sokola, A., Fodritto, F., Dal Toso, G., and Algeri, S., 1987, Functional meaning of tryptophan-induced increase of 5-HT metabolism as clarified by in vivo voltammetry, Brain Res., 411: 89–94.
Dourish, C.T., Hutson, P.H., and Curzon, G., 1985, Characteristics of feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), Brain Res. Bull., 15: 377–384.
During, M.J., Heyes, M.P., Freese, A., Markey, S.P., Martin, J.B., and Roth, R.H., 1989, Quinolinic acid concentrations in striatal extracellular fluid reach potentially neurotoxic levels following systemic L-tryptophan loading, Brain Res., 476: 384–387.
Edvinsson, L., Birath, E., Uddman, R., Lee, T.J.-F., Duerger, D., Mackenzie, E.T., and Scatton, B., 1984, Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine, Acta Physiol. Scand., 121: 291–299.
Elks, M.L., Youngblood, W.W., and Kizer, J.S., 1979, Serotonin synthesis and release in brain slices: independence of tryptophan, Brain Res., 172: 471–486.
Fernstrom, J.D., and Wurtman, R.J., 1971, Brain serotonin content: physiological dependence on plasma tryptophan levels, Science, 173: 149–151.
Foster, A.C., Gill, R., Kemp, J.A., and Woodruff, G.N., 1987, Systemic administration of MK-801 prevents N-methyl-D-aspartäte-induced neuronal degeneration in rat brain. Neurosci. Lett., 76: 307–311.
Gessa, G.L., and Tagliamonte, A., 1974, Serum free tryptophan: control of brain concentrations of tryptophan and of synthesis of 5-hydroxytryptamine, in: “Ciba Foundation Symposium 22: Aromatic Acids in the Brain”, Excerpta Medica, Amsterdam, pp. 207–216.
Globus, M.P.-T., Busto, R., Dietrich, W.D., Martinez, E., Valdes, I., and Ginsberg, M.D., 1988, Intra-ischemic extracellular release of dopamine and glutamate is associated with striatal vulnerability to ischemia, Neurosci. Lett., 91: 36–40.
Hagberg, H., Lehmann, A., Sandberg, M., Nystrom, B., Jacobson, I., and Hamberger, A., 1985, Ischemia-induced shift of inhibitory and excitatory amino acids from intra-to extracellular compartments, J. Cereb. Blood Flow Metab., 5: 413–419.
Hamberger, A., and Nyström, B., 1984, Extra-and intracellular amino acids in the hippocampus during development of hepatic encephalopathy, Neurochem. Res., 9: 1182–1192.
Hardebo, J.E., Emson, P.C., Falck, B., Owman, C., and Rosengren, E., 1980, Enzymes reacted to monoamine transmitter metabolism in brain microvessels, J. Neurochem., 35: 1388–1393.
Hery, F., and Ternaux, J.P., 1981, Regulation of release processes in central serotonergic neurons, J. Physiol. (Paris), 77: 287–301.
Holman, R.B., and Vogt, M., 1972, Release of 5-hydroxytryptamine from caudate nucleus and septum, J. Physiol., 223: 243–254.
Hutson, P.H., and Curzon, G., 1989, Concurrent determination of effects of p-chloroamphetamine on central extracellular 5-hydroxytryptamine concentration and behavior, Br. J. Pharmacol., 96: 801–806.
Hutson, P.H., Sarna, G.S., and Curzon, G., 1986, Neuropharmacokinetic applications of in vivo monitoring techniques, Ann. N.Y. Acad. Sci., 473: 549–552.
Hutson, P.H., Sarna, G.S., O’Connell, M.T. and Curzon, G., 1989, Hippocampal 5-HT synthesis and release in vivo is decreased by infusion of 8-OH-DPAT into the nucleus raphe dorsalis, Neurosci. Lett., in press.
Hutson, P.H., Sarna, G.S., Kantamaneni, B.D., and Curzon, G., 1985, Monitoring the effect of a tryptophan load on brain indole metabolism in freely moving rats by simultaneous cerebrospinal fluid monitoring and brain dialysis, J. Neurochem., 44: 1266–1273.
Hutson, P.H., Sarna, G.S., Sahakian, B.J., Dourish, C.T., and Curzon, G., 1986, Monitoring 5-HT metabolism in the brain of the freely moving rat, Ann. N.Y. Acad. Sci., 473: 321–335.
Kalaria, R.N., and Harik, S.I., 1987, Blood-brain barrier monoamine oxidase: enzyme characterization in cerebral microvessels and other tissues from six mammalian species, including human, J. Neurochem., 49: 856–864.
Kalén, P., Strecker, R.E., Rosengren, E., and Björklund, A., 1988, Endogenous release of neuronal serotonin and 5-hydroxyindoleacetic acid in the caudate-putamen of the rat as revealed by intracerebral dialysis coupled to high-performance liquid chromatography with fluorimetric detection, J. Neurochem., 51: 1422–1435.
Knott, P.J., 1988, Modern methods for studying the release of serotonin, in: “Neuronal Serotonin”, Wiley, New York, pp. 93–127.
Knott, P.J., and Curzon, G., 1974, Effect of increased brain tryptophan on 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the hypothalamus and other brain regions, J. Neurochem., 22: 1065–1071.
Kuhn, D.M., Wolf, W.A., and Youdim, M.B.H., 1985, 5-Hydroxytryptamine release in vivo from a cytoplasmic pool: studies on the behavioral syndrome in reserpinized rats, Br. J. Pharmacol., 84: 121–129.
Lehmann, A., Hagberg, H., Jacobson, I., and Hamberger, A., 1985, Effects of status epilepticus on extracellular amino-acids in the hippocampus, Brain Res., 359: 147–151.
Lerma, J., Herranz, A.S., Herras, O., Abraira, V., and Martin Del Rio, R., 1986, In vivo determination of extracellular concentrations of amino acids in the rat hippocampus, Brain Res., 383: 145–155.
Lookingland, K.J., Shannon, N.J., Chapin, D.S., and Moore, K.E., 1986, Exogenous tryptophan increases synthesis, storage and intraneuronal metabolism of 5-hydroxytryptamine in the rat hypothalamus, J. Neurochem., 47: 205–212.
Manikij, C., Spatz, M., Veki, Y., Nagatsu, I., and Bembry, J., 1984, Cerebrovascular endothelial cell culture: metabolism and synthesis of 5-hydroxytryptamine, J. Neurochem., 43: 316–319.
Mans, A.M., Biebuyck, J.F., Shelly, K., and Hawkins, J.P., 1982, Regional blood-brain barrier permeability to amino acids after portacaval anastomosis, J. Neurochem., 38: 705–717.
Nakayama, H., Ginsberg, M., and Dietrich, W.D., 1988, (S)-Emopamil, a novel calcium channel blocker and serotonin S2 antagonist markedly reduces infarct size following middle cerebral artery occlusion in the rat, Neurology, 38: 1667–1673.
Neckers, L.M., Biggio, G., Moja, E., and Meek, J.L., 1977, Modulation of brain tryptophan hydroxylase activity by brain tryptophan content, J. Pharmacol. Exp. Therap., 201: 110–116.
Ozyurt, E., Graham, D.I., Woodruff, G.N., and MeCulloch, J., 1988, Protective effect of the glutamate antagonist MK-801 in focal cerebral ischemia in the cat, J. Cereb. Blood Flow Metab., 8: 138–143.
Pulsinelli, W.A., Brierley, J.B., and Plum, F., 1982, Temporal profile of neuronal damage in a model of transient forebrain ischemia, Ann. Neurol., 11: 491–498.
Sarna, G.S., Hutson, P.H., and Curzon, G., 1984, Effect of alpha-methylfluorodopa on dopamine metabolites: importance of conjugates and egress, Europ. J. Pharmacol., 100: 343–350.
Sarna, G.S., Hutson, P.H., Tricklebank, M.D., and Curzon, G.S., 1983, Determination of brain 5-hydroxytryptamine turnover in freely moving rats using repeated sampling of cerebrospinal fluid, J. Neurochem., 40: 383–388.
Sarna, G.S., Obrenovitch, T.P., Matsumoto, T., Symon, L., and Curzon, G., 1989, Differential effect of cerebral ischaemia on dopamine and serotonin release as determined by in vivo brain dialysis, J. Cereb. Blood Flow Metab., in press.
Sarna, G.S., Tricklebank, M.D., Kantamaneni, B.D., Hunt, A., Patel, A.J., and Curzon, G., 1982, Effect of age on variables influencing the supply of tryptophan to the brain, J. Neurochem., 39: 1283–1290.
Schwartz, D.H., McClane, S., Hernandez, L., and Hoebel, B.G., 1989, Feeding increases extracellular serotonin in the lateral hypothalamus of the rat as measured by microdialysis, Brain Res., 479: 349–354.
Sharp, T., Bramwell, S.R., and Grahame-Smith, D., 1989, 5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis, Br. J. Pharmacol., 96: 283–290.
Sleight, A.J., Marsden, C.A., Martin, K.F., and Palfreyman, M.G., 1988, Relationship between extracellular 5-hydroxytryptamine and behaviour following monoamine oxidase inhibition and L-tryptophan, Br. J. Pharmacol., 93: 303–310.
Steinbusch, H.W.M., 1984, Serotonin-immunoreactive neurones and their projections in the CNS, in: “Handbook of Chemical Neuroanatomy, Vol. 3”, Björklund, A., Hökfelt, T., and Kuhar, M.J., eds., Elsevier, Amsterdam, pp. 68–125.
Suter, H.A., and Collard, K.J., 1983, The regulation of 5-hydroxytryptamine release from superfused synaptosomes by 5-hydroxytryptamine and its immediate precursors, Neurochem. Res., 8: 723–730.
Takeuchi, Y., Kimura, H., and Sano, Y., 1982, Immunohistochemical demonstration of serotonin-containing nerve fibers in the cerebellum, Cell Tiss. Res., 226: 1–12.
Ternaux, J.P., Hery, F., Hamon, N., Bourgoin, S., and Glowinski, J., 1977, 5-HT release from ependymal surface of the caudate nucleus in ‘encephale isolé’ cats, Brain Res., 132: 575–579.
Tossmann, V., and Ungerstedt, U., 1986, Microdialysis in the study of extracellular levels of amino acids in the rat brain, Acta Physiol. Scand., 128: 9–14.
Tracqui, P., Morot-Gaudry, Y., Staub, J.F., Brezillon, P., Perault-Staub, A.M., Bourgoin, S., and Hamon, M., 1983, Model of brain serotonin metabolism, II. Physiological Interpretation, Am. J. Physiol., 244: R206–R215.
Ungerstedt, U., and Pycock, C.H., 1974, Functional correlates of dopamine neurotransmission, Bull. Schweiz. Akad. Med. Wiss., 30: 44–55.
Westerink, B.H.C., Damsma, G., Rollema, H., De Vries, J.B., and Horn, A.S., 1987, Scope and limitations of in vivo brain dialysis: a comparison of its applications to various neurotransmitter systems, Life Sci., 41: 1763–1776.
Westerink, B.H.C., and De Vries, J.B., 1988, Characterization of in vivo dopamine release determined by brain microdialysis after acute and subchronic implantations: methodological aspects, J. Neurochem., 51: 683–687.
Wolf, W.A., Youdim, M.B.H., and Kuhn, D.M., 1985, Does brain 5-HIAA indicate serotonin release or monoamine oxidase activity?, Eur. J. Pharmacol., 109: 381–387.
Zetterström, T., Brundin, P., Gage, F.H., Sharp, T., Isacson, O., Dunnett, S.B., Ungerstedt, U., and Björklund, A., 1986, Brain Res., 362: 344–349.
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Sarna, G. (1991). Brain Indole Metabolism Assessed Using in Vivo Dialysis. In: Schwarcz, R., Young, S.N., Brown, R.R. (eds) Kynurenine and Serotonin Pathways. Advances in Experimental Medicine and Biology, vol 294. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5952-4_6
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