Abstract
Portal-systemic encephalopathy (PSE) is associated with increased brain turnover of serotonin (5-hydroxytryptamine; 5-HT). Despite this metabolic increase, neuronal release of 5-HT is unaltered in neocortex of portacaval shunted (PCS) rats. In the present study, frontal neocortical extracellular 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) levels were determined in PCS rats and sham-operated controls prior to, as well as, after acute challenge with L-tryptophan (L-TRP; a bolus dose of 280 mg/kg i.p. followed by 5 consecutive hourly doses of 50 mg/kg). Neither basal 5-HT nor 5-HIAA extracellular levels were significantly altered in PCS rats compared to controls. L-TRP administration resulted in unaltered extracellular 5-HT but elevated 5-HIAA levels in PCS and sham rats. These findings do not suggest that changes in brain neuronal 5-HT release play any major functional role in the pathogenesis of chronic PSE. The present data also emphasize the importance of distinguishing between brain 5-HT metabolism and brain 5-HT release.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bengtsson, F., Gage, F. H., Jeppsson, B., Nobin, A., and Rosengren, E. (1985). Brain monoamine metabolism and behaviour in portacaval shunted rats.Exp. Neurol. 90:21–35.
Bengtsson, F., Bugge, M., Brun, A., Falck, B., Henriksson, K. G., and Nobin, A. (1988). The impact of time after portacaval shunt in the rat on behaviour, brain serotonin, and brain and muscle histology.J. Neurol. Sci. 83:109–122.
Bengtsson, F., Bugge, M., and Nobin, A. (1989). Hepatocerebral dysfunction and brain serotonin. In (R.F. Butterworth and G. Pomier Layrargues, eds.),Hepatic encephalopathy: Pathophysiology and Treatment, Humana Press, Clifton, NJ, pp. 355–387.
Bengtsson, F., Bugge, M., Johansen, K. H., and Butterworth, R. F. (1991). Brain tryptophan hydroxylation in the portacaval shunted rat: a hypothesis for the regulation of serotonin turnoverin vivo.J. Neurochem. 56:1069–1074.
Bengtsson, F. (1992). Neurotransmission failure in hepatic encephalopathy involving the combined action of different brain tryptophan-related pathology: a speculative synthesis. In (I. Ishiguro, T. Nagatsu, and Y. Nagamura, eds.),Advances in tryptophan research 1992, Fujita Health University Press, Toyoake, Japan, pp. 303–308.
Bergqvist, P.B.F., Vogels, B.A.P.M., Bosman, D.K., Maas, M.A.W., Hjorth, S., Chamuleau, R.A.F.M., and Bengtsson, F. (1995). Neocortical dialysate monoamines of rats after acute, subacute, and chronic liver shunt.J. Neurochem. 64:1238–1244.
Bergqvist, P.B.F., Heyes, M.P., Apelqvist, G., Butterworth, R.F., and Bengtsson, F. (1996). Brain extracellular quinolinic acid in chronic experimental hepatic encephalopathy as assessed byin vivo microdialysis: Acute effects of L-tryptophan.Neuropsychopharmacology In press.
Carboni, E., Cadoni, C., Tanda, G.L., and Di Chiara, G. (1989). Calcium-dependent, tetrodotoxin-sensitive stimulation of cortical serotonin release after a tryptophan load.J. Neurochem. 53:976–978.
Coppen, A., Prange, A.J. Jr., Whybrow, P.C., and Noguera, R. (1972). Abnormalities of indoleamines in affective disorders.Arch. Gen. Psychiat. 26:474–478.
De Simoni, M.G., Sokola, A., Fodritto, F., Dal Toso, G., and Algri, S. (1987). Functional meaning of tryptophan-induced increase of 5-HT metabolism as clarified byin vivo voltammetry.Brain Res. 411:89–94.
Fernstrom, J.D. (1977). Effects of the diet on brain neurotransmitters.Metabolism 26:207–223.
Fischer, J.E., Yoshimura, N., Aguirre, A., James, J.H., Cummings, M.G., Abel, R.M., and Deindoerfer, F. (1974). Plasma amino acids in patients with hepatic encephalopathy. Effects of amino acid infusions.Am. J. Surg. 127:40–47.
Grahame-Smith, D.G. (1971). Studiesin 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.
Grahame-Smith, D.G. (1973). Does the total turnover of brain 5-HT reflect the functional activity of 5-HT in brain? In (J. Barchas and E. Usdin, eds.),Serotonin and Behavior, Academic Press, New York, NY, pp 5–7.
Hjorth, S., and Sharp, T. (1993).In vivo microdialysis evidence for central serotonin1A and serotonin1B autoreceptor blocking properties of the beta adrenoceptor antagonist (−)penbutolol.J. Pharmacol. Exp. Ther. 265:707–712.
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 sampling and brain dialysis.J. Neurochem. 44:1266–1273.
Joyce, J.N., Shane, A., Lexow, N., Winokur, A., Casanova, M.F., and Kleiman, J.E. (1993). Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics.Neuropsychopharmacology 8:315–336.
Kalén, P., Kokaia, M., Lindvall, O., and Björklund, A. (1988). Basic characteristics of noradrenaline release in the hippocampus of intact and 6-hydroxydopamine-lesioned rats as studied byin vivo microdialysis.Brain Res. 474:374–379.
Lee, S.H., and Fisher, B. (1961). Portocaval shunt in the rat.Surgery 50:668–672.
Mans, A.M., Biebuyck, J.F., Davis, D.W., and Hawkins, R.A. (1984). Portacaval anastomosis: brain and plasma metabolite abnormalities and the effect of nutritional therapy.J. Neurochem. 43:697–705.
Meeusen, R., Thorré, K., Sarre, S., De Meirleir, K., Ebinger, G., and Michotte, Y. (1995). The effect of exercise and L-tryptophan administration on extracellular serotonin metabolism in rat hippocampus.Soc. Neurosci. Abstr. 21:1691.
Sarna, G.S., Hutson, P.H., O'Conell, M.T., and Curzon, G. (1991). Effect of tryptophan on extracellular concentrations of tryptophan and 5-hydroxyindoleacetic acid in the striatum and cerebellum.J. Neurochem. 56:1564–1568.
Schröder, R., Müller, O., and Bircher, J. (1985). The portacaval and splenocaval shunt in the normal rat. A morphometric and functional reevaluation.J. Hepatol. 1:107–123.
Schwartz, D.H., Hernandez, L., and Hoebel, B.G. (1990). Tryptophan increases extracellular serotonin in the lateral hypothalamus of food-deprived rats.Brain Res. Bull. 25:803–807.
Sharp, T., Bramwell, S.R., and Grahame-Smith, D.G. (1992). Effect of acute administration of L-tryptophan on the release of 5-HT in rat hippocampus in relation to serotonergic neuronal activity: anin vivo microdialysis study.Life Sci. 50:1215–1223.
Shields, P.J., and Eccleston, D. (1973). Evidence for the synthesis and storage of 5-hydroxytryptamine in two separate pools in the brain.J. Neurochem. 20:881–888.
Westerink, B.H.C., and De Vries, J.B. (1991). Effect of precursor loading on the synthesis rate and release of dopamine and serotonin in the striatum: A microdialysis study in conscious rats.J. Neurochem. 56:228–233.
Willner, P. (1985). Antidepressants and serotonergic neurotransmission: An intergrative review.Psychopharmacology 85:387–404.
Young, S.N., and Teff, K.L. (1989). Tryptophan availability, 5HT synthesis and 5HT function.Prog. Neuro-Psychopharmacol. Biol. Psychiat. 13:373–379.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bergqvist, P.B.F., Hjorth, S., Apelqvist, G. et al. Acute effects of L-tryptophan on brain extracellular 5-HT and 5-HIAA levels in chronic experimental portal-systemic encephalopathy. Metab Brain Dis 11, 269–278 (1996). https://doi.org/10.1007/BF02237963
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02237963