Skip to main content
SpringerLink
Log in
Book cover

Advances in Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy pp 1–33Cite as

Brain Tryptophan Perturbation in Hepatic Encephalopathy: Implications for Effects by Neuropsychoactive Drugs in Clinical Practice

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 420))

Abstract

The syndromes encountered within the term metabolic encephalopathy may be defined as “any metabolic disease that disrupts normal cerebral function” (Conn and Bircher, 1988). In the case of liver dysfunction, the terms hepatic encephalopathy (HE) or portal-systemic encephalopthy (PSE) are frequently used. In the human and clinical situation, these HE/PSE disorders are recognized as acute, chronic or, most commonly, acute-on-chronic events. The central nervous system (CNS) processes accompanying the patient suffering from HE/PSE probably include a mixture of reversible as well as irreversible changes of euronal function (Victor et al. 1965; Victor 1974, 1979; see also Conn and Lieberthal, 1979). Thus, clinical HE/PSE, which almost inexclusively have included previous or even ongoing exposure to e.g. liver affecting agents, like those related to a variety of acute or chronic infectious or immunological processes, as well as intake of liver toxins such as ethanol. Since the chronic abuse of alcohol is not an uncommon major cause for a subsequently appearing liver cirrhosis, in turn related to the etiology chronic PSE in many clinical cases by blood vessel collateral development bypassing the liver parenchyma, it should be kept in mind that this type of abuse will most certainly exert effects of its own on the CNS in patients with chronic PSE involving aspects of acute, chronic as well as acute-on-chronic CNS effects of ethanol concomitantly to the encephalopathy component provided by the “isolated” PSE per se. Of course, in the clinical setting the isolated effects on the brain of chronic PSE is almost impossible to purify in scientific terms whereas, however, this pure type of chronic PSE may be identified in experimental in vivo models available such as most prominently evidenced by the advent of the surgically induced end-to-side portacaval shunt (PCS) in the rat (Lee and Fisher, 1961).

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adell, A. and Artigas, F., 1991, Differential effects of clomipramine given locally or systemically on extracellular5-hydroxytryptamine in raphe nuclei and frontal cortex. An in vivo brain microdialysis study. Naunyn-Schmiedeberg’s Arch. Pharnzacol. 343: 237–244.

    CAS  Google Scholar 

  • Adell, A., Carceller, A., and Artigas, F., 1991, Regional distribution of extracellular 5-hydroxytryptamine ands-hydroxyindoleacetic acid in the brain of freely moving rats. J. Neurochem. 56: 709–712.

    Article  PubMed  CAS  Google Scholar 

  • Adell, A., Sarna, GS., Hutson, PH., and Curzon, G., 1989, An in vivo dialysis and behavioural study of the release of 5-HT by p-chloroamphetamine in reserpine-treated rats. Br. J. Pharmac. 97: 206–212.

    Article  CAS  Google Scholar 

  • Adell, A., Carceller, A., and Artigas, F., 1993, In vivo brain dialysis study of the somatodendritic release of serotonin in the raphe nuclei of the rat: effects of 8-hydroxy-2-(di-n-propylamino)tetralin. J. Neurochem. 60: 1673–1681.

    Article  PubMed  CAS  Google Scholar 

  • Aghajanian, G.K. and Haigler, H.J., 1975, Hallucinogenic indoleamines: preferential action upon presynaptic serotonin receptors. Psychopharmacol. Comm. 1: 619–629.

    CAS  Google Scholar 

  • Aghajanian, G.K., 1978, Feedback regulation of central monoaminergic neurons: evidence from single cell recording studies. In (Youdim MBH, Lovenberg W, Sharman DF, and Lagnado JR. eds), Essays in Neurochemistry and Neuropharmacology. New York, John Wiley & Sons. pp. 1–32.

    Google Scholar 

  • Alexander, J.J., Banerjee, P., Dawson, G., and Tonsgard, J.H., 1995, Hyperammonemia increases serotonin IA receptor expression in both rat hippocampus and a transfected hippocampal cell line, HN2-5. J. Neurosci. Res. 41: 105–110.

    Article  PubMed  CAS  Google Scholar 

  • Apelqvist, G., Hindfelt, B., Andersson, G., and Bengtsson, F., 1996a, Diurnal and gender effects by chronic portacaval shunting in rats on spontaneous locomotor and rearing activities in an open-field. Submitted.

    Google Scholar 

  • Apelqvist, G., Bergqvist, P.B.F., Larsson, B., Bugge, M., and Bengtsson, F., 1996b, Regional brain serotonin receptor changes in chronic experimental hepatic encephalopathy. Submitted.

    Google Scholar 

  • Arendt, J., 1988, Melatonin. Clin. Endocrinol. 29: 205-229.

    Article  CAS  Google Scholar 

  • Arendt, J., 1995, Melatonin and the Mammalian Brain. London, Chapman and Hill.

    Google Scholar 

  • Artigas, F., 1993, 5-HTIA receptor antagonists in combination therapy. 5-HT and antidepressants: new views from microdialysis studies. Trends Pharrnacol. Sci. 14: 262.

    Article  CAS  Google Scholar 

  • Aschcroft, G.W., Eccleston, D., and Crawford, T.B.B., 1965, 5-Hydroxyindole metabolism in rat brain. A study of intermediate metabolism using the technique of tryptophan loading-I. Methods. J. Neurochem. 12: 483–492.

    Article  Google Scholar 

  • Auerbach, S.B., Minzenberg, M.J., and Wilkinson, L.O., 1989, Extracellular serotonin and 5hydroxyindoleacetic acid in hypothalamus of the unanesthetized rat measured by in vivo microdialysis coupled to high-performance liquid chromatography with electrochemical detection: dialysate serotonin reflects neuronal release. Brain Res. 499: 281–290.

    Article  PubMed  CAS  Google Scholar 

  • Auerbach, S.B., Lundberg, J.F., and Hjorth, S., 1995, Differential inhibition of serotonin release by 5-HT and NA reuptake blockers after systemic administration. Neurophannacology 34: 89–96.

    Article  CAS  Google Scholar 

  • Badawy, A.A-B., Morgan, C.J., Lane, J., Dhaliwal, K., and Bradley, DM., 1989, Liver tryptophan pyrrolase. A major determinant of the lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL mice. Biochem. J. 264: 597–599.

    PubMed  CAS  Google Scholar 

  • Baldessarini, R.J. and Fischer, J.E., 1973, Serotonin metabolism in rat brain after surgical diversion of the portal venous circulation. Nature New Biol. 245: 25–27.

    Article  PubMed  CAS  Google Scholar 

  • Baldessarini, R.J. and Fischer, J.E., 1978, Trace amines and alternative neurotransmitters in the central nervous system. Biochem. Pharrnacol. 27: 621–626.

    Article  CAS  Google Scholar 

  • Basile, A.S., Jones, E.A., and Skolnick, P., 1991, The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands. Pharmacol. Rev. 43: 28–71.

    Google Scholar 

  • Basile, A.S., Saito, K., Al-Mardini, H., Record, C.O., Hughes, R.D., Harrison, P., Williams R, Li Y, and Heyes MP., 1995, The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy. Gastroenterology 108: 818–823.

    Article  PubMed  CAS  Google Scholar 

  • Batshaw, M.L., Robinson, M.B., Hyland, K., Djali, S., and Heyes, M.P., 1993, Quinolinic acid in children with congenital hyperammonemia. Ann. Neurol. 34: 676–681.

    Article  PubMed  CAS  Google Scholar 

  • Baumann, P. and Larsen, P., 1995, The pharmacokinetics of citalopram. Rev. Contemp. Pharmacother. 6: 287–295.

    CAS  Google Scholar 

  • Baumgarten, H.G., Victor, S.J., and Lovenberg, W., 1973, Effect of intraventricular injection of 5,7- dihydroxytryptamine on regional tryptophan hydroxylase of rat brain. J. Neurochem. 21: 251–253.

    Article  PubMed  CAS  Google Scholar 

  • Beadle, G.W., Mitchell, H.K., and Nyc, J.F., 1947, Kynurenine as an intermediate in the formation of nicotinic acid from tryptophane by Neurospora. Proc. Natl. Acad. Sci. 33: 155–158.

    Article  PubMed  CAS  Google Scholar 

  • Beaubernard, C., Salomon, F., Grange, D., Thangapregassam, M.J., and Bismuth, J., 1977, Experimental hepaticencephalopathy. Changes of the level of wakefulness in the rat with portacaval shunt. Biomedicine 27: 169–171.

    PubMed  CAS  Google Scholar 

  • Beck, O., Eriksson, C.J.P., Kiinamaa, K., and Lundman, A., 1986, 5-hydroxyindoleacetic acid and 5Hydroxytryptophol levels in rat brain: effects of ethanol, pyrazole, cyanamide and disulfiram treatment. Drug and Alcohol Dependence 16: 303–308.

    Article  PubMed  CAS  Google Scholar 

  • Beck, O., Lundman, A., and Jonsson, G., 1987, 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid levels in rat brain: effects of various drugs affecting serotonergic transmitter mechanisms. J. Neural Transm. 69: 287–298.

    Article  PubMed  CAS  Google Scholar 

  • Beck, O., Helander, A., Carlsson, S., and Borg, S., 1995, Changes in serotonin metabolism during treatment with the aldehyde dehydrogenase inhibitors disulfiram and cyanamide. Pharmacol. Toxicol. 77: 323–326.

    Article  PubMed  CAS  Google Scholar 

  • Bel, N. and Artigas, F., 1992, Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study. Eur. J. Pharmacol. 229: 101–103.

    Article  PubMed  CAS  Google Scholar 

  • Bengtsson, F., Gage, F.H., Jeppsson, B., Nobin, A., and Rosengren, E., 1985, Brain monoamine metabolism and behavior in portacaval-shunted rats. Exp. Neurol. 90: 21–35.

    Article  PubMed  CAS  Google Scholar 

  • Bengtsson, F., Nobin, A., Falck, B., Gage, F.H., and Jeppsson, B., 1986, Portacaval shunt in the rat: selective alterations in behavior and brain serotonin. Pharmacol. Biochem. Behay. 24: 1611–1616.

    Article  CAS  Google Scholar 

  • Bengtsson, F., Bugge, M., Hansson, L., Fyge, K., Jeppsson, B., and Nobin, A., 1987a, Serotonin metabolism in the central nervous system following sepsis or portacaval shunt in the rat. J. Surg. Res. 43: 420–429.

    Article  CAS  Google Scholar 

  • Bengtsson, F., Bugge, M., Vagianos, C., Jeppsson, B., and Nobin, A., 1987b, Brain serotonin metabolism and behavior in rats with carbon tetrachloride-induced liver cirrhosis. Res. Exp. Med. 187: 429–438.

    Article  CAS  Google Scholar 

  • Bengtsson, F., Bugge, M., Brun, A., Falck, B., Henriksson, K.G., and Nobin, A., 1988a, The impact of time after portacaval shunt in the rat on behavior, brain serotonin, and brain and muscle histology. J. Neurolog. Sci. 83: 109–122.

    Article  CAS  Google Scholar 

  • Bengtsson, F., Nobin, A., Falck, B., Gage, F.H., and Jeppsson, B., 1988b, Effect of oral branched chain amino acids on behavior and brain serotonin metabolism in portacaval shunted rats. World J. Surg. 12: 246–254.

    Article  CAS  Google Scholar 

  • Bengtsson, F., Bugge, M., Hall, H., and Nobin, A., 1989a, Brain 5-HT1 and 5-HT2 binding sites following portacaval shunt in the rat. Res. Exp. Med. 189: 249–256.

    Article  CAS  Google Scholar 

  • Bengtsson, F., Bugge, M., and Nobin, A., 1989b, Hepatocerebral dysfunction and brain serotonin. In (Butterworth RF and Pomier Layrargues G, eds), Hepatic Encephalopathy: Pathophysiology and Treatment. Clifton, NJ, The Humana Press, Inc. pp. 355–385.

    Google Scholar 

  • 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 turnover in vivo. J. Neurochem. 56: 1069–1074.

    Article  PubMed  CAS  Google Scholar 

  • Bengtsson, F., 1992, Neurotransmission failure in hepatic encephalopathy involving the combined action of different brain tryptophan-related pathology: a speculative synthesis. In (Ishiguro I, Kido R, Nagatsu T, Nagamura Y, and Ohta Y, eds), Advances in Tryptophan Research 1992. Toyoake, Japan, Fujita Health University Press. pp. 303–308.

    Google Scholar 

  • Bengtsson, F. and Bergqvist, P.B.F., 1996, Neuropsychiatrie implications of brain tryptophan: Perturbations appearing in hepatic encephalopathy. In (Filippini GA, Costa CVL, and Bertazzo A, eds), Recent Advances in Tryptophan Research. New York, NY, Plenum Publ. Corp. pp. 387–395.

    Chapter  Google Scholar 

  • Bergeron, M., Pomier Layrargues, G., and Butterworth, RF., 1989a, Aromatic and branched-chain amino acids in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Metab. Brain Dis. 4: 169–176.

    Article  CAS  Google Scholar 

  • Bergeron, M., Reader, T.A., Pomier Layrargues, G., and Butterworth, R.F., 1989b, Monoamines and metabolites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Neurochem. Res. 14: 853–859.

    Article  CAS  Google Scholar 

  • Bergeron, M., Swain, M.S., Reader, T.A., Grondin, L., and Butterworth, R.F., 1990, Effect of ammonia on brain serotonin metabolism in relation to function in the portacaval shunted rat. J. Neurochem. 55: 222–229.

    Article  PubMed  CAS  Google Scholar 

  • Bergeron, M., Reader, T.A., and Butterworth. RF., 1991, Early changes of serotonin turnover in brain following portacaval anastomosis: Relation to altered sleep patterns and diurnal rhythms. In (Bengtsson F, Jeppsson B, Almdal T, and Vilstrup H, eds), Progress in Hepatic Encephalopathy and Metabolic Nitrogen Exchange. Boca Raton, FL, CRC Press, Inc. pp. 219–232.

    Google Scholar 

  • Bergeron, M., Swain, M.S., Reader, T.A., and Butterworth, R.F., 1995, Regional alterations of dopamine and its metabolites in rat brain following portacaval anastomosis. Neurochem. Res. 20: 79–86.

    Article  PubMed  CAS  Google Scholar 

  • Bergonzi, P., Bianco, A., Mazza, A., and Mennuni, G., 1978, Night sleep organization in patients with severe hepatic failure. Its modifications after L-DOPA treatment. Eur. Neural. 17: 271–275.

    Article  CAS  Google Scholar 

  • Bergqvist, P.B.F., Werner, E.R., Apelqvist, G., Bugge, M., Wachter, H., and Bengtsson, F., 1995a, Brain biopterin metabolism in chronic experimental hepatic encephalopathy. Metab. Brain Dis. 10: 143–157.

    Article  CAS  Google Scholar 

  • Bergqvist, P.B.F., Heyes, M.P., Bugge, M., and Bengtsson, F., 1995b, Brain quinolinic acid in chronic experimental hepatic encephalopathy: Effects of an exogenous ammonium acetate challenge. J. Neurochem. 65: 2235–2240.

    Article  CAS  Google Scholar 

  • 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., 1995c, Neocortical dialysate monoamines of rats after acute, subacute, and chronic liver shunt. J. Neurochem. 64: 1238–1244.

    Article  CAS  Google Scholar 

  • Bergqvist, P.B.F., Heyes, M.P., Apelqvist, G., Butterworth, R.F., and Bengtsson, F., 1996a, Brain extracellular quinolinic acid in chronic experimental hepatic encephalopathy as assessed by in vivo microdialysis: Acute effects of L-tryptophan. Neuropsychophannacology, 15: 382–389.

    Article  CAS  Google Scholar 

  • Bergqvist, P.B.F., Hjorth, S., Apelqvist, G., and Bengtsson, F., 1996b, Acute effects of L-tryptophan on brain extracellular 5-HT and 5-HIAA in chronic experimental portal-systemic encephalopathy. Metab. Brain Dis., 11: 269–278.

    Article  CAS  Google Scholar 

  • Bergqvist, P.B.F., Hjorth, S., Audet, R., Apelqvist, G., Bengtsson, F., and Butterworth, R.F., 1996c, Ammonium acetate challenge in experimental hepatic encephalopathy induces a transient increase of brain 5-HT release in vivo. Eur. Neuropsychopharmacology, In press.

    Google Scholar 

  • Bergqvist, PBF, Some, M, Apelqvist, G, Helander, A, and Bengtsson, F., 1996d, Elevated brain 5- hydroxytryptophol levels in chronic experimental portal-systemic encephalopathy. Submitted.

    Google Scholar 

  • Bergqvist, P.B.F., Hjorth, S., Apelqvist, G., and Bengtsson, F., 1997a, Potassium-evoked neuronal serotonin release in experimental portal-systemic encephalopathy. Submitted.

    Google Scholar 

  • Bergqvist, P.B.F., Hjorth, S., Wikell, C., Apelqvist, G., and Bengtsson, F., 1997b, p-Chloroamphetamineand d-fenfluramine induced brain serotonin release in experimental portal-systemic encephalopathy. Submitted.

    Google Scholar 

  • Bergqvist, P.B.F., Wikell, C., Hjorth, S., Apelqvist, G., and Bengtsson, F., 1997c, Citalopram and release of brain serotonin in experimental portal-systemic encephalopathy: Implications for the clinical use of selective serotonin reuptake inhibitors in liver insufficiency. Submitted.

    Google Scholar 

  • Bessman, S.P. and Bessman, A.N., 1955, The cerebral and peripheral uptake of ammonia in liver disease with an hypothesis for the mechanism of hepatic coma. J. Clin. Invest. 34: 622–628.

    Article  PubMed  CAS  Google Scholar 

  • Blier, P., de Montigny, C., and Tardif, D., 1984, Effects of the two antidepressant drugs mianserin and indalpine on the serotonergic system: single-cell studies in the rat. Psychopharmacology 84: 242–249.

    Article  PubMed  CAS  Google Scholar 

  • Bloxam, D.L. and Curzon, G., 1978, A study of proposed determinants of brain tryptophan concentration in rat after portocaval anastomosis or sham operation. J. Neurochem. 31: 1255–1263.

    Article  PubMed  CAS  Google Scholar 

  • Bonanno, G., Fassio, A., Severi, P., Ruelle, A., and Raiteri, M., 1994, Fenfluramine releases serotonin from human brain nerve endings by a dual mechanism. J. Neurochem. 63: 1163–1166.

    Article  PubMed  CAS  Google Scholar 

  • Borowsky, B. and Hoffman, B.J., 1995, Neurotransmitter transporters: molecular biology, function, and regulation. Int. Rev. Neurobiol. 38: 139–199.

    Article  PubMed  CAS  Google Scholar 

  • Brodie, B.B., Pletscher, A., and Shore, PA., 1955, Evidence that serotonin has a role in brain function. Science 122: 968.

    Article  PubMed  CAS  Google Scholar 

  • Bucci, L., Cardelli, M., Chiavarelli, R., Massotti, M., and Morisi, G., 1980, Behavioral, electroencephalographic, and biochemical changes in porta-cava shunted rats. Intern. J. Neuroscience 10: 129–134.

    CAS  Google Scholar 

  • Bucci, L., Ioppolo, A., Chiavarelli, R., and Bigotti, A., 1982, The central-nervous-system toxicity of long- term oral administration of L-tryptophan to porto-caval-shunted rats. Br. J. exp. Path. 63: 235–241.

    CAS  Google Scholar 

  • Bugge, M., Bengtsson, F., Nobin, A., Holmin, T., Jeppsson, B., Hultberg, B., Falck, B., and Herlin, P., 1986, Amino acids and indoleamines in the brain after infusion of branched-chain amino acids to rats with liver ischemia. J. Parent. Ent. Nutr. 10: 474–478.

    Article  CAS  Google Scholar 

  • Bugge, M., Bengtsson, F., Nobin, A., Hall, H., Wedel, I., Jeppsson, B., and Herlin, P., 1989a, Serotonin receptors in the brain following total hepatoectomy in rats treated with branched-chain amino acids. J. Parent. Ent. Nutr. 13: 235–239.

    Article  CAS  Google Scholar 

  • Bugge, M., Bengtsson, F., Nobin, A., Jeppsson, B., Hultberg, B., Jonung, T., and Herlin, P., 1989b, The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats. Res. Exp. Med. 189: 101–111.

    Article  CAS  Google Scholar 

  • Bulat, M., Iskric, S., Stancic, L., Kveder, S., and Zivkovic, B., 1970, The formation of 5-hydroxytryptophol from exogenous 5-hydroxytryptamine in cat spinal cord in vivo. J. Pharm. Phannacol. 22: 67–68.

    Article  CAS  Google Scholar 

  • Butterworth, R.F., Giguère, J.F., Michaud, J., Lovoie, J., and Layrargues, G.P., 1987, Arnmonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem. Pathol. 6: 1–12.

    Article  PubMed  CAS  Google Scholar 

  • Butterworth, R.F., Girard, G., and Giguère, J-F., 1988, Regional differences in the capacity for ammonia removal by brain following portocaval anastomosis. J. Neurochem. 51: 486–490.

    Article  PubMed  CAS  Google Scholar 

  • Butterworth, R.F., 1992a, Evidence that hepatic encephalopthy results from a defect of glutamatergic synaptic regulation. Mol. Neuropharmacol. 2: 229–232.

    CAS  Google Scholar 

  • Butterworth, R.F., 1992b, Pathogenesis and treatment of portal-systemic encephalopathy: An update. Dig. Dis. Sci. 37: 321–327.

    Article  CAS  Google Scholar 

  • Butterworth, R.F., 1993, Portal-systemic encephalopathy: A disorder of neuron-astrocytic metabolic trafficking. Dev. Neurosci. 15: 313–319.

    Article  PubMed  CAS  Google Scholar 

  • Butterworth, R.F., 1994, Hepatic encephalopathy. In (Arias IM, Boyer JL, Fausto N, Jakoby WB, Schachter DA, and Shafritz DA, eds), The Liver: Biology and Pathology. New York, N.Y., Raven Press, Ltd., pp. 1193–1208.

    Google Scholar 

  • Butterworth, R.F., 1996, Neuroactive amino acids in hepatic encephalopathy. Metab. Brain Dis. 11: 165–173.

    Article  PubMed  CAS  Google Scholar 

  • Cahill, G.M. and Besharse, J.C., 1995, Circadian rhythmicity in vertebrate retinas: regulation by a photoreceptor oscillator. Prog. Ret. Eye Res. 14: 267–291.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Carboni, E. and Di Chiara, G., 1989, Serotonin release estimated by transcortical dialysis in freely-moving rats. Neuroscience 32: 637–645.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson, A. and Lindqvist, M., 1978, Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino-acids in rat brain. Naunyn-Schmiedeberg’s Arch. Pharmacol. 303: 157–164.

    CAS  Google Scholar 

  • Cascino, A., Cangiano, C., Fiaccadori, F., Ghinelli, F., Merli, M., Pelosi, G., Riggio, O., Rossi-Fanelli, F., Sacchini, D., Stortoni, M., and Capocaccia, L.. 1982, Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy. Dig. Dis. Sci. 27: 828–832.

    Article  PubMed  CAS  Google Scholar 

  • Cascio, C.S., and Kellar, K.J., 1983, Characterization of [3H]tryptamine binding sites in brain. Eur. J. Pharmacol. 95: 31–39.

    Article  PubMed  CAS  Google Scholar 

  • Cheifetz, S. and Warsh, J.J., 1980, Occurence and distribution of 5-hydroxytryptophol in the rat. J. Neurochem. 34:1093–1099.

    Article  PubMed  CAS  Google Scholar 

  • Chesselet, M.-F., 1984, Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis. Neuroscience 12: 347–375.

    Article  PubMed  CAS  Google Scholar 

  • Clemens, J.A., Sawyer, B.D., and Cerimele, B., 1977, Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion. Endocrinology 100: 692–698.

    Article  PubMed  CAS  Google Scholar 

  • Conn, H.O., and Lieberthal, M.M., 1979, The hepatic coma syndromes and lactulose. Baltimore, MD, The Williams & Williams Co.

    Google Scholar 

  • Conn, H.O. and Bircher, J., 1988, Hepatic Encephalopathy: Management with Lactulose and Related Carbohydrates. East Lansing, Michigan, Medi-Ed Press.

    Google Scholar 

  • Costa, E., and Meek, J.L., 1974, Regulation of biosynthesis of catecholamines and serotonin in the CNS. Ann. Rev. Pharmacol. 14: 491–511.

    Article  CAS  Google Scholar 

  • Crinquette, J-F., Boschat, M., Rapin, J-R., Delorme, M-L., and Opolon, P., 1982, Early changes in blood- brain barrier permeability after porto-caval shunt and liver ischaemia. Clin. Physiol. 2: 241–250.

    Article  PubMed  CAS  Google Scholar 

  • Crossley, I.R. and Williams, R., 1984, Progress in the treatment of chronic portasystemic encephalopathy. Gut 20: 85–98.

    Article  Google Scholar 

  • Cuilleret, G., Pomier Layrargues, G., Pons, F., Cadilhac, J., and Michel, H., 1980, Changes in brain catecholamine levels in human cirrhotic hepatic encephalopathy. Gut 21: 565–569.

    Article  PubMed  CAS  Google Scholar 

  • Cummings, M.G., Soeters, P.B., James, J.H., Keane, J.M., and Fischer, J.E., 1976a, Regional brain indoleamine metabolism following chronic portacaval anastomosis in the rat. J. Neurochem. 27: 501–509.

    Article  CAS  Google Scholar 

  • Cummings, M.G., Soeters, P.B., James, J.H., Keane, J.M., and Fischer, J.E., 1976b, Regional brain study of indoleamine metabolism in the rat in acute hepatic failure. J. Neurochem. 27: 741–746.

    Article  CAS  Google Scholar 

  • Curzon, G., Kantamaneni, B.D., Winch, J., Rojas-Bueno, A., Murray-Lyon, I.M., and Williams, R., 1973, Plasma and brain tryptophan changes in experimental acute hepatic failure. J. Neurochem. 21: 137–145.

    Article  PubMed  CAS  Google Scholar 

  • Curzon, G., Kantamaneni, B.D., Fernando, J.C., Woods, M.S., and Cavanagh, J.B., 1975, Effects of chronic porto-caval anastomosis on brain tryptophan, tyrosine and 5-hydroxytryptamine. J. Neurochem. 24: 1065–1070.

    Article  PubMed  CAS  Google Scholar 

  • Curzon, G., and Marsden, C.A., 1975, Metabolism of a tryptophan load in the hypothalamus and other brain regions. J. Neurochem. 25: 251–256.

    Article  PubMed  CAS  Google Scholar 

  • Curzon, G., Fernando, J.C.R., and Marsden, C.A., 1978, 5-Hydroxytryptamine: the effects of impaired synthesis on its metabolism and release in rat. Br. J. Pharmac. 63: 62–-634.

    Article  CAS  Google Scholar 

  • Curzon, G., 1986, Serotonin neurochemistry revisited: a new look at some old axioms. Neurochem. Int. 8: 155–159.

    CAS  Google Scholar 

  • Dalhoff, K., Almdal, T.P., Bjerrum, K., Keiding, S., Mengel, H., and Lund, J., 1991, Pharmacokinetics of paroxetine in patients with cirrhosis. Eur. J. Clin. Pharmacol. 41: 351–354.

    Article  PubMed  CAS  Google Scholar 

  • Davis, V.E., Cashaw, J.L., Huff, J.A., and Brown, H., 1966, Identification of 5-hydroxytryptophol as a serotonin metabolite in man. Proc. Soc. Exp. Biol. Med. 122: 890–893.

    PubMed  CAS  Google Scholar 

  • de Montigny, C., Blier, P., and Chaput, Y., 1984, Electrophysiologically-identified serotonin receptors in the rat CNS. Effect of antidepressant treatment. Neuropharniacology 23: 1511–1520.

    Article  Google Scholar 

  • de Parada, M.P., Parada, M.A., Pothos, E., and Hoebel, B.G., 1995, d-Fenfluramine, but not dnorfenfluramine, uses calcium to increase extracellular serotonin. Life Sci. 56: 415–420.

    Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Deguchi, T., 1975, Ontogenesis of a biological clock for serotonin:acetyl coenzyme A N-acetyltransferase in pineal gland of rat. Proc. Natl. Acad. Sci. 72: 2814–2818.

    Article  PubMed  CAS  Google Scholar 

  • Descarries, L., and Beaudet, A., 1983, The use of radioautography for investigating transmitter-specific neurons. In (Björklund A and Hökfelt T, eds), Handbook of Chemical Neuroanatomy. Vol 1: Methods in Chemical Neuroanatonzy. Amsterdam, Elsevier, pp. 286–364.

    Google Scholar 

  • DeVane, C.L., Laizure, S.C., Stewart, J.T., Kolts, B.E., Ryerson, E.G., Miller, R.L., and Lai, A.A., 1990, Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. J. Clin. Psychopharmacol. 10: 328–332.

    Article  PubMed  CAS  Google Scholar 

  • DeVane, C.L., 1994, Pharmacokinetics of newer antidepressants: clinical relevance. Am. J. Med. 97(suppl 6A): 13S–23S.

    Article  PubMed  CAS  Google Scholar 

  • Dewhurst, W.G., and McKim, HR., 1980, Pharmacological effects of p-chloroamphetamine with respect to current amine hypotheses of affective disorders. Neuropsychobiology 6: 66–71.

    Article  PubMed  CAS  Google Scholar 

  • Di Chiara, G., 1990, Brain dialysis of neurotransmitters: a commentary. J. Neurosci. Meth. 34: 29–34.

    Article  Google Scholar 

  • Diggory, G.L., Ceasar, P.M., Hazelby, D., and Taylor, K.T., 1979, Endogenous 5-hydroxytryptophol in mouse brain. J. Neurochem. 32: 1323–1325.

    Article  PubMed  CAS  Google Scholar 

  • Doogan, D.P., and Caillard, V., 1988, Sertraline: A new antidepressant. J. Clin. Psychiat. 49(8, suppl): 4651.

    Google Scholar 

  • Dooley, D.J., and Quock, R.M., 1976, Tryptamine and 5-hydroxytryptamine-induced hypothermia in mice. J. Pharni. Pharmacol. 28: 775–776.

    Article  CAS  Google Scholar 

  • Dreshfield, L.J., Wong, D.T., Perry, K.W., and Engleman, E.A., 1996, Enhancement of fluoxetine-dependent increase of extracellular serotonin (5-HT) levels by (-)-pindolol, an antagonist at 5-HTIA receptors. Neurochem. Res. 21: 557–562.

    Article  PubMed  CAS  Google Scholar 

  • Eccleston, D., Aschcroft, G.W., and Crawford, T.B.B., 1965, 5-Hydroxyindole metabolism in rat brain. A study of intermediate metabolism using the technique of tryptophan loading-II. Applications and drug studies. J. Neurochem. 12: 493–503.

    Article  Google Scholar 

  • Eccleston, D., Aschcroft, G.W., Crawford, T.B.B., Stanton, J.B., Wood, D., and McTurk, P.H., 1970, Effect of tryptophan administration on 5HIAA in cerebrospinal fluid in man. J. Neurol. Neurosurg. Psychiat. 33: 269–272.

    Article  PubMed  CAS  Google Scholar 

  • El Mansari, M., and Blier, P., 1996, Functional characterization of 5-HTID autoreceptors on the modulation of 5-HT release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex. Br. J. Pharmacol. 118: 681–689.

    Article  PubMed  CAS  Google Scholar 

  • Elks, M.L., Youngblood, W.W., and Kizer, J.S., 1979, Serotonin synthesis and release in brain slices: independece of tryptophan. Brain Res. 172: 471–486.

    Article  PubMed  CAS  Google Scholar 

  • Ellinger, A., 1904, Die Entstehung der Kynurensäure. Z. Physiol. Chem. 43: 325–337.

    Article  Google Scholar 

  • Engel, G., Göthert, M., Hoyer, D., Schlicker, E., and Hillenbrand, K., 1986, Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HTIB binding sites. Naunyn-Schmiedeberg’s Arch. Pharmacol. 332: 1–7.

    CAS  Google Scholar 

  • Ennis, C., Kemp, J.D., and Cox, B., 1981, Characterisation of inhibitory 5-hydroxytryptamine receptors that modulate dopamine release in the striatum. J. Neurochem. 36: 1515–1520.

    Article  PubMed  CAS  Google Scholar 

  • Ennis, C. and Cox, B., 1982, Pharmacological evidence for the existence of two distinct serotonin receptors in rat brain. Neuropharmacology 21: 41–44.

    Article  PubMed  CAS  Google Scholar 

  • Erecinska, M., Pastuszko, A., Wilson, D.F., and Nelson, D., 1987, Ammonia-induced release of neurotransmitters from rat brain synaptosomes: differences between the effects on amines and amino acids. J. Neurochem. 49: 1258–1265.

    Article  PubMed  CAS  Google Scholar 

  • Faraj, B.A., Camp, V.M., Ansley, J.D., Scott, J., Ali, F.M., and Malveaux, E.J., 1981, Evidence for central hypertyraminemia in hepatic encephalopathy. J. Clin. Invest. 67: 395–402.

    Article  PubMed  CAS  Google Scholar 

  • Feldstein, A., Chang, F.H., and Kucharski, J.M., 1970, Tryptophol, 5-hydroxytryptophol and 5methoxytryptophol induced sleep in mice. Life Sci. 9: 323–329.

    Article  PubMed  CAS  Google Scholar 

  • Fernstrom, J.D., and Wurtman, R.J., 1971, Brain serotonin content: physiological dependence on plasma tryptophan levels. Science 173: 149–151.

    Article  PubMed  CAS  Google Scholar 

  • Ferré, S., and Artigas, F., 1993, Dopamine D2 receptor-mediated regulation of serotonin extracellular concentration in the dorsal raphe nucleus of freely moving rats. J. Neurochem. 61: 772–775.

    Article  PubMed  Google Scholar 

  • Ferrier, I.N., Arendt, J., Johnstone, E.C., and Crow, T.J., 1982, Reduced nocturnal melatonin secretion in chronic schizophrenia: relationship to body weight. Clin. Endocrinol. 17: 181–187.

    CAS  Google Scholar 

  • Ferry, N., Bernard, N., Cuisinaud, G., Rougier, P., Trepo, C., and Sassard, J., 1994, Influence of hepatic impairment on the pharmacokinetics of nefazodone and two of its metabolites after single and multiple oral doses. Fundam. Clin. Pharmacol. 8: 463–473.

    CAS  Google Scholar 

  • Fischer, J.E., and Baldessarini, R.J., 1971, False neurotransmitters and hepatic failure. The Lancet ii: 75–79.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Fischer, J.E., and Baldessarini, R.J., 1976, Pathogenesis and therapy of hepatic coma. In (Popper H and Schaffner F, eds), Progress in Liver Diseases. New York, Grune & Stratton., pp. 363–397.

    Google Scholar 

  • Fornai, C.A., Metzler, C.W., Gallegos, R.A., Veasey, S.C., McCreary, A.C., and Jacobs, B.L., 1996, WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135. J. Pharmacol. Exp. Ther. 278: 752–762.

    Google Scholar 

  • Freese, A., Swartz, K.J., During, M.J., and Martin, J.B., 1990, Kynurenine metabolites of tryptophan: Implications for neurologic diseases. Neurology 40: 691–695.

    Article  PubMed  CAS  Google Scholar 

  • Friedman, P.A., Kappelman. A.H., and Kaufman. S., 1972, Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 247: 4165–4173.

    PubMed  CAS  Google Scholar 

  • Fu, L.H.W., Hayashi, S., and Toda, N., 1980, Effects of 5-hydroxytryptophol, a 5-hydroxytryptamine metabolite, on isolated cerebral arteries of the dog. Br. J. Pharmac. 68: 17–18.

    Article  CAS  Google Scholar 

  • Fukushima, T., and Nixon, J.C., 1980, Analysis of reduced forms of biopterin in biological tissues and fluids. Anal. Biochem. 102: 176–188.

    Article  PubMed  CAS  Google Scholar 

  • Fuller, R.W., and Wong, D.T., 1990, Serotonin uptake and serotonin uptake inhibition. N.Y. Acad. Sci. 600: 68–78.

    Article  CAS  Google Scholar 

  • Fuxe, K., Butcher, L.L., and Engel, J., 1971, DL-5-hydroxytryptophan-induced changes in central monoamine neurons after peripheral decarboxylase inhibition. J. Pharm. Pharmacol. 23: 420–424.

    Article  PubMed  CAS  Google Scholar 

  • Gallego, A., and Lorente de No, R., 1947, On the effect of several monovalent ions upon frog nerve. J. Cell. Comp. Physiol. 29: 189–206.

    Article  CAS  Google Scholar 

  • Garfinkel, D., Laudon, M., Nof, D., and Zisapel, N., 1995, Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 346: 541–544.

    Article  PubMed  CAS  Google Scholar 

  • Gartside, S.E., Cowen, P.J., and Sharp, T., 1992, Effect of 5-hydroxy-L-tryptophan on the release of 5-HT in rat hypothalamus in vivo as measured by microdialysis. Neuropharmacology 31: 9–14.

    Article  PubMed  CAS  Google Scholar 

  • George, J., Murray, M., Byth, K., and Farrell, G.C., 1995, Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology 21: 120–128.

    PubMed  CAS  Google Scholar 

  • Gholson, R.K., Ueda, I., Ogasawara, N., and Henderson, L.M., 1964, The enzymatic conversion of quinolinate to nicotinic acid mononucleotide in mammalian liver. J. Biol. Chem. 239: 1208–1214.

    PubMed  CAS  Google Scholar 

  • Gibson, C.J., Deikel, S.M., Young, S.N., and Binik, Y.M., 1982, Behavioural and biochemical effects of tryptophan, tyrosine and phenylalanine in mice. Psychopharamacology 76: 118–121.

    Article  CAS  Google Scholar 

  • Gobbi, M., Frittoli, E., and Mennini, T., 1990, The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain synaptosomes is not mediated by the α2B-adrenoceptor subtype. Naunyn-Schmiedeberg’s Arch. Pharmacol. 342: 382–386.

    CAS  Google Scholar 

  • Goodnick, P.J., 1991, Pharmacokinetics of second generation antidepressants: fluoxetine. Psychopharmacol. Bull. 27: 503–512.

    PubMed  CAS  Google Scholar 

  • Grahame-Smith, D.G., 1971, 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.

    Article  PubMed  CAS  Google Scholar 

  • Grahame-Smith, D.G., 1973, Does the total turnover of brain 5-HT reflect the functional activity of 5-HT in brain. In (Barchas J and Usdin E, eds), Serotinin and Behavior. New York, NY, Academic Press., pp. 5–7.

    Google Scholar 

  • Grahame-Smith, D.G., 1974, How important is the synthesis of brain 5-hydroxytryptamine in the physiological control of its central function? Adv. Biochem. Psychopharmacol. 10: 83–91.

    CAS  Google Scholar 

  • Gullino, P., Winitz, M., Birnbaum, S.M., Cornfield, J., Otey, M.C., and Greenstein, J.P., 1956, Studies on the metabolism of amino acids and related compounds in vivo. I. Toxicity of essential amino acids, individually and in mixtures, and the protective effect of L-arginine. Arch. Biochem. Biophys. 64: 319–332.

    Article  PubMed  CAS  Google Scholar 

  • Hale, A.S., 1993, New antidepressants: use in high-risk patients. J. Clin. Psychiat. 54: 61–70.

    Google Scholar 

  • Héry, F., and Ternaux, J.P., 1981, Regulation of release processes in central serotoninergic neurons. J. Physiol. (Paris) 77: 287–301.

    Google Scholar 

  • Heslop, K.E., and Curzon, G., 1994, Depletion and repletion of cortical tissue and dialysate 5-HT after reserpine. Neuropharmacology 33: 567–573.

    Article  PubMed  CAS  Google Scholar 

  • Hindfelt, B., Plum, F., and Duffy, T.E., 1977, Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J. Clin. Invest. 59: 386–396.

    Article  PubMed  CAS  Google Scholar 

  • Hirayama, C, 1971, Thryptophan metabolism in liver disease. Clin. Chim. Acta 32: 191–197.

    Article  PubMed  CAS  Google Scholar 

  • Hjorth S, and Sharp, T., 1991, Effect of the 5-HTIA receptor agonist 8-OH-DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis. Life Sci. 48: 1779–1786.

    Article  PubMed  CAS  Google Scholar 

  • Hjorth, S., and Tao, R., 1991, The putative 5-HTIB receptor agonist CP-93,129 supresses rat hippocampal 5-HT release in vivo: comparison with RU 24969. Eur. J. Pharmacol. 209: 249–252.

    Article  PubMed  CAS  Google Scholar 

  • Hjorth, S., 1993, Serotonin 5-HTIB autoreceptor blockade potentiates the ability of the 5-HT reuptake inhibitor citalopram to increase nerve terminal output of 5-HT in vivo: a microdialysis study. J. Neurochem. 60: 776–779.

    Article  PubMed  CAS  Google Scholar 

  • Hjorth, S., and Auerbach, S.B., 1994, Further evidence for the importance of 5-HT autoreceptors in the activation of selective serotonin reuptake inhibitors. Eur. J. Pharmacol. 260: 251–255.

    Article  PubMed  CAS  Google Scholar 

  • Hjorth, S., and Auerbach, S.B., 1996, 5-HTIA autoreceptors and the mode of action of selective serotonin reuptake inhibitors (SSRI). Behay. Brain Res. 73: 281–283.

    Article  CAS  Google Scholar 

  • Hjorth, S., 1996, (-)-Pindolol, but not buspirone, potentaites the citalopram-induced rise in extracellular 5hydroxytryptamine. Eur. J. Pharmacol. 303: 183–186.

    Article  PubMed  CAS  Google Scholar 

  • Holm, E., Uhl, W., and Stamm, S., 1986, Safety of fluvoxamine for patients with chronic liver disease. Adv. Pharmacother. 2: 151–165.

    Google Scholar 

  • Holm, E., Jacob, S., Kortsik, C., Leweling, H., and Fischer, B., 1988, Failure of selective serotonin re-uptake inhibition to worsen the mental state of patients with subclinical hepatic encephalopathy. In (Soeters PB, Wilson JHP, Meijer A.J, and Holm E, eds), Advances in Ammonia Metabolism and Hepatic Encephalopathy. Amsterdam, Elsevier Science Publishers B.V., pp. 474–486.

    Google Scholar 

  • Hoyer, D., Clarke, D.E., Fozard, J.R., Hartig, P.R., Martin, G.R., Mylecharane, E.J., Saxena, P.R., and Humphrey, P.P.A., 1994, VII. International union of pharmacology classification of receptors for 5hydroxytryptamine (serotonin). Pharmacol. Rev. 46: 157–203.

    PubMed  CAS  Google Scholar 

  • Hutson, D.G., Ono, J., Dombro, R.S., Levi, J.U., Livingstone, A., and Zeppa, R., 1979, A longitudinal study of tryptophan involvment in hepatic coma. Am. J. Surg. 137: 235–239.

    Article  PubMed  CAS  Google Scholar 

  • 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. Neurchem. 44: 1266–1273.

    Article  CAS  Google Scholar 

  • 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 8-0H-DPAT into the nucleus raphe dorsalis. Neurosci. Lett. 100: 276–280.

    Article  PubMed  CAS  Google Scholar 

  • Ichiyama, A., Nakamura, S., Nishizuka, Y., and Hayaishi, O., 1968, Tryptophan-5-hydroxylase in mammalian brain. Adv. Pharmacol. 6A: 5–17.

    Article  Google Scholar 

  • Jackson, H.C., Hewitt, K.N., Hutchins, L.J., Cheetham, S.C., and Heal, D.J., 1996, Augmentation of antidepressant action of SSRIs by pindolol may not be explained by 5-HT1A receptor antagonism. Soc. Neurosci. Abstr. 22: 1328.

    Google Scholar 

  • Jacobs, B.L. and Fornai, C.A., 1991, Activity of brain serotonergic neurons in the behaving animal. Pharmacol. Rev. 43: 563–578.

    PubMed  CAS  Google Scholar 

  • James, J.H., Hodgman, J.M., Funovics, J.M., Yoshimura. N., and Fischer, J.E., 1976, Brain tryptophan, plasma free tryptophan and distribution of plasma neutral amino acids. Metabolism 25: 471–476.

    Article  PubMed  CAS  Google Scholar 

  • James, J.H., Escourrou, J., and Fischer, J.E., 1978, Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis. Science 200: 1395–1397.

    Article  PubMed  CAS  Google Scholar 

  • James, J.H., Ziparo, V., Jeppsson, B., and Fischer, J.E., 1979, Hyperammonemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy. Lancet,ii:.772-775.

    Google Scholar 

  • James, S.P., Sack, D.A., Rosenthal, N.E., and Mendelson, W.B., 1990, Melatonin administration in insomnia. Neuropsychopharmacology 3: 19-23.

    PubMed  CAS  Google Scholar 

  • Jellinger, K. and Riederer, P., 1977, Brain monoamines in metabolic (endotoxic) coma. A preliminary biochemical study in human postmortem material. J. Neural Transm. 41: 275–286.

    Article  PubMed  CAS  Google Scholar 

  • Jellinger, K., Riederer, P., Rausch, W.D., and Kothbauer, P., 1978, Brain monoamines in hepatic encephalopathy and other types of metabolic coma. J. Neural Transm. Suppl. 14: 103–120.

    PubMed  CAS  Google Scholar 

  • Jessy, J., Mans, A.M., DeJoseph, M.R., and Hawkins, R.A., 1990, Hyperammonemia causes many of the changes found after portacaval shunting. Biochem. J. 272: 311–317.

    PubMed  CAS  Google Scholar 

  • Johnston, C.A., and Moore, K.E., 1983, Measurement of 5-hydroxytryptamine synthesis and metabolism in selected discrete regions of the rat brain using high performance liquid chromatography and electrochemical detection: pharmacological manipulations. J. Neural Transm. 57: 49–63.

    Article  PubMed  CAS  Google Scholar 

  • Kalén, P., Strecker, R.E., Rosengren, E., and Björklund, A., 1989, Regulation of striatal serotonin release by the lateral habenula-dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and GABA. Brain Res. 492: 187–202.

    Article  PubMed  Google Scholar 

  • Kimelberg, H.K., 1988, Serotonin uptake into astrocytes and its implications. In (Osborne NN and Hamon M, eds), Neuronal Serotonin. John Wiley & Sons, Ltd., pp. 347–365.

    Google Scholar 

  • Klein, D.C. and Weller, J.L., 1970, Indole metabolism in the pineal gland: a circadian rhythm in Nacetyltransferase. Science 169: 1093–1095.

    Article  PubMed  CAS  Google Scholar 

  • Kleven, M.S., Dwoskin, L.P., and Sparber, S.B., 1983, Pharmacological evidence for the existence of multiple functional pools of brain serotonin: analysis of brain perfusate from conscious rats. J. Neurochem. 41: 1143–1149.

    Article  PubMed  CAS  Google Scholar 

  • Knapp, S., and Mandell, A.J., 1984, TRH influences the pterin cofactor-and time-dependent instabilities of rat raphe tryptophan hydroxylase activity assessed under far-from-equilibrium conditions. Neurochem. Int. 6: 801–812.

    Article  PubMed  CAS  Google Scholar 

  • Knell, A.J., Davidson, A.R., Williams, R., Kantamaneni, B.D., and Curzon, G., 1974, Dopamine and serotonin metabolism in hepatic encephalopathy. Br. Med. J. 1: 549–551.

    Article  PubMed  CAS  Google Scholar 

  • Knott, P.J. and Curzon, G., 1974, Effect of increased rat brain tryptophan on 5-hydroxytryptamine and 5- hydroxyindolyl acetic acid in the hypothalamus and other brain regions. J. Neurochem. 22: 1065–1071.

    Article  PubMed  CAS  Google Scholar 

  • Krastev, Z., Terziivanov, D., Vlahov, V, Maleev, A., Greb, W.H., Eckl, K.M., Dierdorf H-D., and Wolf D., 1989, The pharmacokinetics of paroxetine in patients with liver cirrhosis. Acta Psychiatr. Scand. 80(suppl 350): 91–92.

    Google Scholar 

  • Krause, D.N., and Dubocovich, M.L., 1990, Regulatory sites in the melatonin system of mammals. Trends Neurosci. 13: 464–470.

    Article  PubMed  CAS  Google Scholar 

  • Kuhn, D.M., Wolf, W.A., and Youdim, M.B.H., 1985, 5-Hydroxytryptamine release in vivo from a cytoplasmic pool: studies on the 5-HT behavioural syndrome in reserpinized rats. Br. J. Pharmac. 84: 121–129.

    CAS  Google Scholar 

  • Lapin, I.P., 1978, Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice. J. Neural Transm. 42: 37–43.

    Article  PubMed  CAS  Google Scholar 

  • Lapin, I.P., 1981, Kynurenines and seizures. Epilepsia 22:257–265.

    Article  PubMed  CAS  Google Scholar 

  • Lavoie, J., Giguère, J.F., Layrargues, G.P., and Butterworth, R.F., 1987, Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J. Neurochem. 49: 692–697.

    Article  PubMed  CAS  Google Scholar 

  • Lee, S.H. and Fisher, B., 1961, Portacaval shunt in the rat. Surgery 50: 668–672.

    PubMed  CAS  Google Scholar 

  • Levine, R.A., Kuhn, D.M., and Lovenberg, W., 1979, The regional distribution of hydroxylase cofactor in rat brain. J. Neurochem. 32: 1575–1578.

    Article  PubMed  CAS  Google Scholar 

  • Levine, R.A., Zoephel, G.P., Niederwieser, A., and Curtius, H-C., 1987, Entrance of tetrahydrobiopterin derivates in brain after peripheral administration: effect on biogenic amine metabolism. J. Pharmacol. Exp. Ther. 242: 514–522.

    PubMed  CAS  Google Scholar 

  • Lewy, A.J., Wehr, TA., Gold, P.W, and Goodwin, F.K., 1978, Plasma melatonin in manic-depressive illness. In (Usdin E, Kopin II, and Barechas J, eds), Catecholamines: Basic and Clinical Frontiers. Oxford, Pergamon., pp. 1173–1175.

    Google Scholar 

  • Lockwood, A.H., McDonald, J.M., Reiman, R.E., Gelbard, A.S., Laughlin, J.S., Duffy, T.E., and Plum, F., 1979, The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J. Clin. Invest. 63: 449–460.

    Article  PubMed  CAS  Google Scholar 

  • Long, J.B., Youngblood, WY, and Kizer, J.S., 1983, Regional differences in the response of serotonergic neurons in rat CNS to drugs. Eur. J. Pharmacol. 88: 89–97.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Lovenberg, W., Jequier, E., and Sjoerdsma, A., 1967, Tryptophan hydroxylation: measurement in pineal gland, brainstem, and carcinoid tumor. Science 155: 217–219.

    Article  PubMed  CAS  Google Scholar 

  • Maddrey, W.C., and Weber F.L.Jr., 1975, Chronic hepatic encephalopathy. Symposium on Diseases of the Liver, pp. 937–944.

    Google Scholar 

  • Mans, A.M., Saunders, S.J., Kirsch, R.E., and Biebuyck, J.F., 1979, Correlation of plasma and brain amino acid and putative neurotransmitter alterations during acute hepatic coma in the rat. J. Neurochem. 32: 285–292.

    Article  PubMed  CAS  Google Scholar 

  • Mans, A.M., Biebuyck, J.F., Shelly, K., and Hawkins, R.A., 1982, Regional blood-brain barrier permeability to amino acids after portacal anastomosis. J. Neurochem. 38: 705–717.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Mans, A.M. and Hawkins, R.A., 1986, Brain monoamines after portacaval anastomosis. Metab. Brain Dis. 1: 45–52.

    Article  CAS  Google Scholar 

  • Mans, A.M., Consevage, M.W., DeJoseph, M.R., and Hawkins, R.A., 1987, Regional brain monoamines and their metabolites after portacaval shunting. Metab. Brain Dis. 2: 183–193.

    Article  PubMed  CAS  Google Scholar 

  • Mans, A.M., DeJoseph, M.R., Davis, D.W, Villa, J.R., and Hawkins, R.A., 1990, Early establishment of cerebral dysfunction after portacaval shunting. Am. J. Physiol. 259: E104–E110.

    PubMed  CAS  Google Scholar 

  • Marsden, C.A., and Curzon, G., 1976, Studies on the behavioural effects of tryptophan and pchlorophenylalanine. Neuropharmacology 15: 165–171.

    Article  PubMed  CAS  Google Scholar 

  • Martin, G.R. and Humphrey, P.P.A., 1994, Receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature. Neuropharmacology 33: 261–273.

    Article  PubMed  CAS  Google Scholar 

  • Masson, P., and Berger, L., 1923, Sur un nouveau mode de sécrétion interne: La neurocrinie. C. R. Acad. Sci. (Paris) 176: 1748–1750.

    Google Scholar 

  • Matos, F.F., Rollema, H., Brown, J.L., and Basbaum, A.I., 1992, Do opioids evoke the release of serotonin in the spinal cord? An in vivo microdialysis study of the regulation of extracellular serotonin in the rat. Pain 48: 439–447.

    Article  PubMed  CAS  Google Scholar 

  • Matos, F.F., Urban, C., and Yocca, F.D., 1996, Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: raphé control somatodendrtitic and terminal 5-HT release. J. Neural Transm. 103: 173–190.

    Article  PubMed  CAS  Google Scholar 

  • McLennan, H., 1983, Receptors for the excitatory amino acids in the mammalian central nervous system. Prog. Neurobiology. 20: 251–271.

    Article  CAS  Google Scholar 

  • Meek, J.L. and Lofstrandh, S., 1976, Tryptophan hydroxylase in discrete brain nuclei: comparison of activity in vitro and in vivo. Eur. J. Pharmacol. 37: 377–380.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • Melamed, E., Hefti, F., and Wurtman, R.J., 1980, L-3,4-Dihydroxyphenylalanine and L-5-hydroxytryptophan decarboxylase activities in rat striatum: effect of selective destruction of dopaminergic or serotoninergic input. J. Neurochem. 34: 1753–1756.

    Article  PubMed  CAS  Google Scholar 

  • Mennini, T, Borroni, E., Samanin, R., and Garattini, S., 1981, Evidence of the existence of two different intraneuronal pools from which pharmacological agents can release serotonin. Neurochem. Ittt. 3: 289–294.

    Article  CAS  Google Scholar 

  • Miwa, S., Watanabe, Y, and Hayaishi, O., 1985, 6R-L-Erythro-5,6,7,8-tetrahydrobiopterin as a regulator of dopamine and serotonin biosynthesis in the rat brain. Arch. Biochem. Biophys. 239: 234–241.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, D.J., and McLean, A.J., 1995, Clinical pharmacokinetik and pharmacodynamic considerations in patients with liver disease. Clin. Pharmacokinet. 29: 370–391.

    Article  CAS  Google Scholar 

  • Moroni, F., Lombardi, G., Carlà, V, Pellegrini, D., Carassale, G.L., and Cortesini, C., 1986a, Content of quinolinic acid and of other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy. J. Neurochem. 46: 869–874.

    Article  CAS  Google Scholar 

  • Moroni, F., Lombardi, G., Carlà, V, Lal, S., Etienne, P., and Nair, N.P.V., 1986b, Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure. J. Neurochem. 47: 1667–1671.

    Article  CAS  Google Scholar 

  • Morot-Gaudry, Y, Bourgoin, S., and Hamon, M., 1981, Kinetic characteristics of newly synthesized 3H-5-HT in the brain of control and reserpinized mice. Evidence for the heterogeneous distribution of 5-HT in serotoninergic neurons. Naunyn-Schmiedeberg’s Arch. Pharmacol. 316: 311–316.

    CAS  Google Scholar 

  • Mousseau, D.D., 1993, Tryptamine: a metabolite of tryptophan implicated in various neuropsychiatric disorders. Metab. Brain Dis. 8: 1–44.

    Article  CAS  Google Scholar 

  • Mousseau, D.D., Perney, P., Pomier Layrargues, G., and Butterworth, R.F., 1993, Selective loss of palladial dopamine D2 receptor density in hepatic encephalopathy. Neurosci. Lett. 162: 192–196.

    Article  PubMed  CAS  Google Scholar 

  • Mousseau, D.D., and Butterworth, R.F., 1994a, The [3H]tryptamine receptor in human brain: kinetics, distribution, and pharmacologi profile. J. Neurochem. 63: 1052–1059.

    Article  CAS  Google Scholar 

  • Mousseau, D.D., and Butterworth, R.F., 1994b, Current theories on the pathogenesis of hepatic encephalopathy. Exp. Biol. Med. 206: 329–344.

    CAS  Google Scholar 

  • Mousseau, D.D., Pomier Layrargues, G., and Butterworth, R.F., 1994, Region-selective decreases in densities of [3H]tryptanúne binding sites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J. Neurochem. 62: 621–625.

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu, T 1985, Biopterin cofactor and monoamine-synthesizing monooxygenases. In, (Osborne NN, ed), Selected Topics in Neurochemistry. Pergammon., pp. 325–340.

    Google Scholar 

  • Neckers, L.M., Biggio, G., Moja, E., and Meek, J.L., 1977, Modulation of brain tryptophan hydroxylase activity by braintryptophan content. J. Pharamcol. Exp. Ther. 201: 110–116.

    CAS  Google Scholar 

  • Nichol, C.A., Smith, G.K., and Duch, D.S., 1985, Biosynthesis and metabolism of tetrahydrobiopterin and molybdopterin. Ann. Rev. Biochem. 54: 729–764.

    Article  PubMed  CAS  Google Scholar 

  • Norenberg, M.D., 1987, The role of astrocytes in hepatic encephalopathy. Neurochem. Pathol. 6: 13–33.

    Article  PubMed  CAS  Google Scholar 

  • Numazawa, R., Yoshioka, M., Matsumoto, M., Togashi, H., Kemmotsu, O., and Saito, H., 1995, Pharmacological characterization of α2 -adrenoceptor regulated serotonin release in the hippocampus. Neurosci. Lett. 192: 161–164.

    Article  PubMed  CAS  Google Scholar 

  • Ogihara, K., Lowenstein, L.M., and Nakao, K., 1967, Abnormal indole metabolism in hepatic coma. In (Vandenbroucke J, De Groote J, and Standaert LO, eds), Liver Research. Tijdschrift voor Gastroenterologie. Antwerpen, pp. 56–67.

    Google Scholar 

  • Ohta, K., Fukuuchi, Y, Shimazu, K., Komatsumoto, S., Ichijo, M., Araki, N., and Shibata, M., 1994, Presynaptic glutamate receptors facilitate release of norepinephrine and 5-hydroxytryptamine as well as dopamine in the normal and ischemic striatum. J. Auto Nerv. Syst. 49: S195–S202.

    Article  CAS  Google Scholar 

  • Ono, J., Hutson, D.G., Dombro, R.S., Levi, J.U, Livingstone, A, and Zeppa, R., 1978, Tryptophan and hepatic coma. Gastroenterology 74: 196–200.

    PubMed  CAS  Google Scholar 

  • Orlando, R., Benvenuti, C., Mazzo, M., and Palatini, P., 1995, The pharmacokinetics of teniloxazine in healthy subjects and patients with hepatic cirrhosis. Br. J. clin. Pharmac. 39: 445–448.

    Article  CAS  Google Scholar 

  • Palacios, J.M., Waeber, C., Hoyer, D., and Mengod, G., 1990, Distribution of serotonin receptors. Ann. N.Y. Acad. Sci. 600: 36–52.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, WM., 1977, Kinetics of competetive inhibition of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 28: 103–108.

    Article  PubMed  CAS  Google Scholar 

  • Perkins, M.N., and Stone, TW., 1982, An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 247: 184–187.

    Article  PubMed  CAS  Google Scholar 

  • Perkins, M.N., and Stone, TW., 1983a, Pharmacology and regional variations of quinolinic acid-evoked excitations in the rat central nervous system. J. Pharmacol. Exp. Ther. 226: 551–557.

    CAS  Google Scholar 

  • Perkins, M.N., and Stone, TW., 1983b, Quinolinic acid: regional variations in neuronal sensitivity. Brain Res. 259: 172–176.

    Article  CAS  Google Scholar 

  • Perry, K.W., and Fuller, R.W., 1993, Extracellular 5-hydroxytryptamine concentration in rat hypothalamus after administration of fluoxetine plus L-5-hydroxytryptophan. J. Pharm. Pharmacol. 45: 759–761.

    Article  PubMed  CAS  Google Scholar 

  • Peterson, C., Giguere, J.F., Cotman, C.W, and Butterworth, R.F., 1990, Selective loss of N-methyl-Daspartate-sensitive L-[3H]glutamate binding sites in rat brain following portacaval anastomosis. J. Neurochem. 55: 386–390.

    Article  PubMed  CAS  Google Scholar 

  • Pierpaoli, W., and Regelson, W., 1994, Pineal control of aging: Effect of melatonin and pieal grafting on aging mice. Proc. Natl. Acad. Sci. 91: 787–791.

    Article  PubMed  CAS  Google Scholar 

  • Raabe, W., 1987, Synaptic transmission in ammonia intoxication. Neurochem. PathoL 6: 145–166.

    Article  PubMed  CAS  Google Scholar 

  • Rao, V.L.R., Murthy, Ch.R.K., and Butterworth, R.F., 1992, Glutamatergic synaptic dysfunction in hyperammonemic syndromes. Metab. Brain Dis. 7: 1–20.

    Article  PubMed  CAS  Google Scholar 

  • Rao, V.L.R., Giguère, J-F., Pomier Layrargues, G., and Butterworth, R.F., 1993, Increased activities of MAO? and MAOB in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Brain Res. 621: 349–352.

    Article  PubMed  CAS  Google Scholar 

  • Rao, V.L.R., Therrien, G., and Butterworth, R.F., 1994a, Choline acetyltransferase and acetylcholinesterase activities are unchanged in brain in human and experimental portal-systemic encephalopathy. Metab. Brain Dis. 9: 401–407.

    Article  CAS  Google Scholar 

  • Rao, V.L.R., and Butterworth, R.F., 1994b, Alterations of [3H]8-OH-DPAT and [3H]ketanserin binding sites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Neurosci. Lett. 182: 69–72.

    Article  CAS  Google Scholar 

  • Rao, V.L.R., Audet, R.M., and Butterworth, R.F., 1995, Selective alterations of extracellular brain amino acids in relation to function in experimental portal-systemic encephalopathy: results of an in vivo microdialysis study. J. Neurochem. 65: 1221–1228.

    PubMed  CAS  Google Scholar 

  • Reichle, R.M., and Reichle, F.A., 1975, Effect of portacaval shunt and acute hepatic ischemia on brain and liver serotonin and catecholamines. Surg. Forum 26: 413–414.

    PubMed  CAS  Google Scholar 

  • Reinhardt, J.F.Jr. and Wurtman, R.J., 1977, Relation between brain 5-HIAA levels and the release of serotonin into brain synapses. Life Sci. 21: 1741–1746.

    Article  Google Scholar 

  • Robinson, M.B., Heyes, M.P., Anegawa, N.J., Gorry, E., Djali, S., Mellits, E.D., and Batshaw M.L., 1992a, Quinolinate in brain and cerebrospinal fluid in rat models of congenital hyperammonemia. Pediatr. Res. 32: 483–488.

    Article  CAS  Google Scholar 

  • Robinson, M.B., Anegawa, N.J., Gorry, E., Qureshi, I.A, Coyle, J.T, Lucki, I., and Batshaw, M.L., 1992b, Brain serotonin2 and serotoninIA receptors are altered in the congenitally hyperammonemic sparse fur mouse. J. Neurochem. 58: 1016–1022.

    Article  CAS  Google Scholar 

  • Rokicki, W, Rokicki, M., Kaminski, K., Peciak, B., and Gebska, E., 1989, Experimental investigations of the pathomechanism of portal encephalopathy. I. Activity of monoamine oxidase (MAO) in brain cortex and cerebellum of rats after portacaval shunt. Neuropat. Pol. 27: 199–207.

    CAS  Google Scholar 

  • Royer, R.J., Royer-Morrot, M.J., Paille, F., Brraucand, D., Schmitt, J., Defrance, R., and Salvadori, C., 1989, Tianeptine and its main metabolite pharmacokinetics in chronic alcoholism and cirrhosis. Clin. Pharmacokin. 16: 186–191.

    Article  CAS  Google Scholar 

  • Rössle, M., Luft, M., Herz, R., Klein, B., Lehmann, M., and Gerok, W., 1984, Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution. Klin. Wochenschr. 62: 867–875.

    Article  PubMed  Google Scholar 

  • Rössle, M., Herz, R., Klein, B., and Gerok, W., 1986, Tryptophan-Metabolismus bei Lebererkrankungen: eine pharmakokinetische and enzymatische Untersuchung. Klin. Wochenschr. 64: 590–594.

    Article  PubMed  Google Scholar 

  • Sabelli, H.C., and Giardina, WJ., 1970, CNS effects of the aldehyde products of brain monoamines. Biol. Psychiat. 2: 119–139.

    PubMed  CAS  Google Scholar 

  • Salerno, F., Delloco, M., Incerti, P., Uggeri, F., and Beretta, E., 1984, Alterations of plasma and brain tryptophan in hepatic encephalopathy: a study in humans and in experimental animals. In (Capocaccia L, Fischer JE, and Rossi-Fanelli F, eds), Hepatic Encephalopathy in Chronic Liver Failure. NY, Plenum Press, pp. 95–106.

    Chapter  Google Scholar 

  • Sandyk, R., 1990, Possible role of pineal melatonin in the mechanisms of aging. Intern. J. Neuroscience 52: 85–92.

    CAS  Google Scholar 

  • Sarna, G.S., Bradbury, M.W.B., and Cavanagh, J., 1977, Permeability of the blood-brain barrier after portocaval anastomosis in the rat. Brain Res. 138: 550–554.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Sawada, M., Sugimoto, T, Matsuura, S., and Nagatsu, T., 1986, (6R)-Tetrahydrobiopterin increases the activity of tryptophan hydroxylase in rat raphe slices. J. Neurochem. 47: 1544–1547.

    Article  PubMed  CAS  Google Scholar 

  • Schaechter, J.D. and Wurtman, R.J., 1990, Serotonin release varies with brain tryptophan levels. Brain Res. 532: 203–210.

    Article  PubMed  CAS  Google Scholar 

  • Schaub, R.G. and Meyers, K.M., 1975, Evidence for a small functional pool of serotonin in neurohumoral transmission. Res. Commun. Chem. Pathol. Pharmacol. 10: 29–36.

    PubMed  CAS  Google Scholar 

  • Schenker, S. and Mendelson, J.H., 1964, Cerebral adenosine triphosphate in rats with ammonia-induced coma. Am. J. Physiol. 206: 1173–1176.

    PubMed  CAS  Google Scholar 

  • Schenker, S., McCandless, D.W, Brophy, E., and Lewis, M.S., 1967, Studies on the intracerebral toxicity of ammonia. J. Clin. Invest. 46: 838–848.

    Article  PubMed  CAS  Google Scholar 

  • Schenker, S., and Hoyumpa, A.M.Jr., 1984, Pathophysiology of hepatic encephalopathy. Phys. Med. Sept: 99–121.

    Google Scholar 

  • Schenker, S., Bergstrom, R.F., Wolen, R.L., and Lemberger, L., 1988, Fluoxetine disposition and elimination in cirrhosis. Clin. Pharmacol. Ther. 44: 353–359.

    Article  PubMed  CAS  Google Scholar 

  • Schoedon, G., Troppmair, J., Fontana, A, Huber, C., Curtius, H-C., and Niederwieser, A., 1987, Biosynthesis and metabolism of pterins in peripheral blood mononuclear cells and leukemia lines of man and mouse. Eur. J. Biochem. 166: 303–310.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Sharp, T, Bramwell, S.R., Clark, D., and Grahame-Smith, D.G., 1989, In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity. J. Neurochem. 53: 234–240.

    Article  PubMed  CAS  Google Scholar 

  • Sharp, T., and Hjorth S., 1990, Application of brain microdialysis to study the pharmacology of the 5-HTIA autoreceptor. J. Neurosci. Meth. 34: 83–90.

    Article  CAS  Google Scholar 

  • 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 serotoninergic neuronal activity: an in vivo microdialysis study. Life Sci. 50: 1215–1223.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Shore, P.A and Giachetti, A., 1978, Reserpine: basic and clinical pharmacology. In (Iversen L.L. and Snyder SH, eds), Handbook of Psychopharmacology. New York, Plenum Press., pp. 197–219.

    Chapter  Google Scholar 

  • Simert, G., Nobin, A, Rosengren, E., and Vang, J., 1978, Neurotransmitter changes in the rat brain after portacaval anastomosis. Eur. Burg. Res. 10: 73–85.

    Article  CAS  Google Scholar 

  • Sleight, AJ., Marsden, C.A, Martin, K.F., and Palfreyman, M.G., 1988, Relationship between extracellular 5-hydroxytryptamine and behaviour following monoamino oxidase inhibition and L-tryptophan. Br. J. Pharntacol. 93: 303–310.

    Article  CAS  Google Scholar 

  • Smith, AR., Rossi-Fanelli, F., Ziparo, V, James, J.H., Perelle, BA, and Fischer, J.E., 1978, Alterations in plasma and CSF amino acids, amines and metabolites in hepatic coma. Ann. Surg. 187: 343–350.

    Article  PubMed  CAS  Google Scholar 

  • Soeters, P.B., and de Boer, J., 1984, Why are plasma branched chain amino acid levels diminished in patients with liver cirrhosis? In (Adibi SA, Fekl W, Langenbeck U, and Schauder P, eds), Branced Chain Amino and Keto Acids in Health and Disease. Basel, Karger., pp. 483–496.

    Google Scholar 

  • Sonne, J., 1996, Drug metabolism in liver disease: implications for therapeutic drug monitoring. Ther. Drug Monit. 18: 397–401.

    Article  PubMed  CAS  Google Scholar 

  • Sourkes, T.L., 1977, Enzymology of aromatic amino acid decarboxylase. In (Usdin E, Weiner N, and Youdim MBH., eds), Structure and Function of Monoamine Enzymes. New York, Marcel Dekker Inc., pp. 477–495.

    Google Scholar 

  • Steindl, P.E., Gottstein, J., and Blei, AT., 1995a, Disruption of circadian locomotor activity in rats after portacaval anastomosis is not gender dependent. Hepatology 22: 1763–1768

    Article  CAS  Google Scholar 

  • Steindl, P.E., Finn, B., Bendok, B., Rothke, S., Zee, P.C., and Blei, A.T., 1995b, Disruption of the diurnal rhythm of plasma melatonin in cirrhosis. Ann. Intern. Med. 123: 274–277.

    CAS  Google Scholar 

  • Stoeckel, K., Pfefen, J.P., Mayersohn, M., Schoerlin, M.P., Andressen, C., Ohnhaus E.E., Frey, F., and Guentert, TW., 1990, Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidey function. Acta Psychiatr. Scand. Suppl 360: 94–97.

    CAS  Google Scholar 

  • Stone, T.W., and Perkins, M.N., 1981, Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. Eur. J. Pharmacol. 72: 411–412.

    Article  PubMed  CAS  Google Scholar 

  • Stone, T.W., 1993, Neuropharmacology of quinolinic and kynurenic acids. Pharrrtacol. Rev. 45: 309–379.

    CAS  Google Scholar 

  • Sulzer, D., and Rayport, S., 1990, Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action. Neuron 5: 797–808.

    Article  PubMed  CAS  Google Scholar 

  • Sulzer, D., Pothos, E., Minjung Sung, H., Maidment, N.T, Hoebel, B.G., and Rayport, S., 1992, Weak base model of amphetamine action. Ann. N.Y. Acad. Sci. 654: 525–528.

    Article  PubMed  CAS  Google Scholar 

  • Sulzer, D., Maidment, N.T, and Rayport, S., 1993, Amphetamine and other weak bases act to promote reverse transport of dopamine in ventral midbrain neurons. J. Neurochem. 60: 527–535.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Swain, M.S., Blei, AT, Butterworth, R.F., and Kraig, R.P., 1991, Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats. Regulatory Intergrative Comp. Physiol. 30: R1491–R1496.

    Google Scholar 

  • Szerb, J.C. and Butterworth, R.F., 1992, Effect of ammonium ions on synaptic transmission in the mammalian central nervous system. Prog. Neurol. 39: 135–153.

    Article  CAS  Google Scholar 

  • Taborsky, R.G., 1971, 5-Hydroxytryptophol: evidence for its having physiological properties. Experientia 27: 929–930.

    Article  PubMed  CAS  Google Scholar 

  • Takada, A, Grdisa, M., Diksic, M., Gjedde, A, and Yamamoto, YL., 1993, Rapid steady-state analysis of blood-brain transfer of L-Trp in rat, with special reference to the plasma protein binding. Neurochem. hit. 23: 351–359.

    Article  CAS  Google Scholar 

  • Tamir, H., Theoharides, TC., Gershon, M.D., and Askenase, P.W., 1982, Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of [3H]serotonin. J. Cell Biol. 93: 638–647.

    Article  PubMed  CAS  Google Scholar 

  • Tao, R. and Hjorth, S., 1992, a2-Adrenoceptor modulation of rat ventral hippocampal 5-hydroxytryptamine release in vivo. Naunyn-Schnziedeberg’s Arch. Pharnsacol. 345: 137–143.

    CAS  Google Scholar 

  • Tao, R., and Auerbach, S.B., 1996, Differential effect of NMDA on extracellular serotonin in rat midbrain raphe and forebrain sites. J. Neurochem. 66: 1067–1075.

    Article  PubMed  CAS  Google Scholar 

  • Tappaz, M.L., and Pujol, J-F., 1980, Estimation of the rate of tryptophan hydroxylation in vivo: a sensitive microassay in discrete rat brain nuclei. J. Neurochem. 34: 933–940.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, B.K. and Basbaum, AI., 1995, Neurochemical characterization of extracellular serotonin in the rostra] ventromedial medulla and its modulation by noxious stimuli. J. Neurochem. 65: 578–589.

    Article  PubMed  CAS  Google Scholar 

  • Ternaux, J.P., Boireau, A, Bourgoin, S., Hamon, M., Hery, F., and Glowinski, J., 1976, In vivo release of 5-HT in the lateral ventricle of the rat: effects of 5-hydroxytryptophan and tryptophan. Brain Res. 101: 533–548.

    Article  PubMed  CAS  Google Scholar 

  • Theander, B., Apelqvist, G., Bugge, M., Andersson, G., Hindfelt, B., and Bengtsson, F., 1996, Gender and diurnal effect on specific open-field behavioral patterns in the portacaval shunted rat. Metab. Brain Dis. In Press.

    Google Scholar 

  • Thorré, K., Sarre, S., Twahirwa, E., Meeusen, R., Ebinger, G., Haemers, A, and Michotte, Y., 1996, Effect of L-tryptophan, L-5-hydroxytryptophan and L-tryptophan prodrugs on the extracellular levels of 5-HT and 5-HIAA in the hippocampus of the rat using microdialysis. Eur. J. Pharm. Sci. 4: 247–256.

    Article  Google Scholar 

  • Tracqui, P., Morot-Gaudry, Y, Staub, J.F., Brézillon, P., Perault-Staub, AM., Bourgoin, S., and Hamon, M., 1983, Model of brain serotonin metabolism. II. Physiological interpretation. Am. J. Physiol. 244: R206–R215.

    PubMed  CAS  Google Scholar 

  • Tricklebank, M.D., Smart, J.L., Bloxam, D.L., and Curzon, G., 1978, Effects of chronic experimental liver dysfunction and L-tryptophan on behavior in the rat. Phartnacol. Biochem. Behay. 9: 181–189.

    Article  CAS  Google Scholar 

  • Tyce, G.M., Flock, E.V, Owen, C.AJr., Stobie, G.H.C., and David, C., 1967, 5-Hydroxyindole metabolism in the brain after hepatectomy. Biochem. Pharmacol16: 979–992.

    Article  PubMed  CAS  Google Scholar 

  • Uribe, M., Farca, A., Marquez, M.A., Garcia-Ramos, G., and Guevara, L., 1979, Treatment of chronic portal systemic encephalopathy with bromocriptine. A double-blind controlled trial. Gastroenterology 76: 1347–1351.

    PubMed  CAS  Google Scholar 

  • Victor, M., Adams, R.D., and Cole, M., 1965, The acquired (non-Wilsonian) type of chronic hepatocerebral degeneration. Medicine 44: 345–396.

    Article  PubMed  CAS  Google Scholar 

  • Victor, M., 1974, Neurologic changes in liver disease. In (Plum F, ed), Brain Dysfunction in Metabolic Disorders. New York, N.Y., Raven Press, pp. 1–12.

    Google Scholar 

  • Victor M., 1979, Neurologic disorders due to alholism and malnutrition. In (Baker A and Baker L., eds), Clinical Neurology. Hagerstown, Harper & Row.

    Google Scholar 

  • Werner, E.R., Werner-Felmayer, G., Fuchs, D., Hausen, A, Reibnegger, G., and Wachter, H., 1989, Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine-2,3-dioxygenase activity in human cells and cell lines by interferon-γ. Biochem. J. 262: 861–866.

    PubMed  CAS  Google Scholar 

  • Werner-Felmayer, G., Prast, H., Werner, E.R., Philippu, A, and Wachter, H., 1993, Induction of GTP cyclohydrolase I by bacteriel lipopolysaccharide in the rat. FEBS Lett. 322: 223–226.

    Article  PubMed  CAS  Google Scholar 

  • Westerink, B.H.C., Damsma, G., Rollema, H., de Vries, J.B., and Horn, AS., 1987, Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. Life Sci. 41: 1763–1776.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Wetterberg, L., Arendt, J., Paunier, L., Sizonenko, P.C., van Donselaar, W, and Heyden, T., 1976, Human serum melatonin changes during the menstrual cycle. J. Clin. Endocrinol. Metab. 42: 185–188.

    Article  PubMed  CAS  Google Scholar 

  • Wetterberg, L., Aperia, B., Beck-Friis, J., Kjellman, B.F., Ljunggren, J-G., Nilsonne, A, Petterson, U, Tham, A, and Undén, F., 1982, Melatonin and cortisol levels in psychiatric illness. The Lancet ii: 100.

    Google Scholar 

  • Whetsell, WO.Jr., and Schwarcz, R., 1989, Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system. Neurosci. Lett. 97: 271–275.

    Article  PubMed  CAS  Google Scholar 

  • Whittaker, VP., and Roed, I.S., 1982, New insights into vesicle recycling in a model choliergic system. In (Bradford HF., ed), Neurotransmitter Interaction and Compartmentation. New York, Plenum Press., pp. 151–173.

    Google Scholar 

  • Whitton, P.S., Biggs, C.S., Pearce, B.R., and Fowler, L.J., 1992, MK-801 increases extracellular 5hydroxytryptamine in rat hippocampus and striatum in vivo. J. Neurochem. 58: 1573–1575.

    Article  PubMed  CAS  Google Scholar 

  • Wichems, C.H., Hollingsworth, C.K., and Bennett, BA., 1995, Release of serotonin induced by 3,4methylenedioxymethamphetamine (MDMA) and other substituted amphetamines in cultured fetal raphe neurons: further evidence for calcium-independent mechanisms of release. Brain Res. 695: 10–18.

    Article  PubMed  CAS  Google Scholar 

  • Wolf, W.A., and Kuhn, D.M., 1986, Uptake and release of tryptophan and serotonin: an HPLC method to study the flux of endogenous 5-hydroxyindoles through synaptosomes. J. Neurochem. 46: 61–67.

    Article  PubMed  CAS  Google Scholar 

  • Wong, D.T, Horng, J.S., Bymaster, F.P., Hauser, K.L., and Molloy, B.B., 1974, A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. Life Sci. 15: 471–479.

    Article  PubMed  CAS  Google Scholar 

  • Wu, P.H., and Boulton, AA., 1987, Distribution and metabolism of tryptamine in rat brain. Can. J. Biochem. 51: 1104–1112.

    Google Scholar 

  • Yoshioka, M., Matsumoto, M., Togashi, H., Smith, C.B., and Saito, H., 1993, Opioid receptor regulation of 5-hydroxytryptamine release from the rat hippocampus measured by in vivo microdialysis. Brain Res. 613: 74–79.

    Article  PubMed  CAS  Google Scholar 

  • Young, S.N., Lal, S., Sourkes, TL., Feldmuller, F., Aronoff, A, and Martin, 7.B., 1975, Relationships between tryptophan in serum and CSF, and 5-hydroxyindoleacetic acid in CSF of man: effect of cirrhosis of liver and probenecid administration. J. Neurol. Neurosurg. Psychiat. 38: 322–330.

    Article  PubMed  CAS  Google Scholar 

  • Young, S.N. and Sourkes, TL., 1977, Tryptophan in the central nervous system: regulation and significance. Adv. Neurochem. 2: 133–191.

    Article  CAS  Google Scholar 

  • Young, S.N., Anderson, G.M., and Purdy, WC., 1980, Indoleamine metabolism in rat brain studied through measurements of tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in cerebrospinal fluid. J. Neurochem. 34: 309–315.

    Article  PubMed  CAS  Google Scholar 

  • Young, S.N., and Lai, S., 1980, CNS tryptamine metabolism in hepatic coma. J. Neural Transm. 47: 153–161.

    Article  PubMed  CAS  Google Scholar 

  • Young, S.N., and Anderson, G.M., 1982, Factors influencing melatonin, 5-hydroxytryptophol, 5hydroxyindoleacetic acid, 5-hydroxytryptamine and tryptophan in rat pineal glands. Neuroendocrinology 35: 464–468.

    Article  PubMed  CAS  Google Scholar 

  • Young, S.N., and Teff, K.L., 1989, Tryptophan availability, 5HT synthesis and 5HT function. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 13: 373–379.

    Article  CAS  Google Scholar 

  • Zee, P.C., Mehta, R., Turek, F.W., and Blei, AT., 1991, Portacaval anastomosis disrupts circadian locomotor activity and pineal melatonin rhythms in rats. Brain Res. 560: 17–22.

    Article  PubMed  CAS  Google Scholar 

  • Zieve, L., and Olsen, R.L., 1977, Can hepatic coma be caused by a reduction of brain noradrenaline or dopamine. Gut 18: 688–691.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, Lund University Hospital, S-221 85, Lund, Sweden

    Finn Bengtsson, Peter B. F. Bergqvist & Gustav Apelqvist

Authors
  1. Finn Bengtsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter B. F. Bergqvist
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gustav Apelqvist
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Instituto de Investigaciones Citologicas de la F. V. I. B., Valencia, Spain

    Vicente Felipo  & Santiago Grisolía  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Plenum Press, New York

About this chapter

Cite this chapter

Bengtsson, F., Bergqvist, P.B.F., Apelqvist, G. (1997). Brain Tryptophan Perturbation in Hepatic Encephalopathy: Implications for Effects by Neuropsychoactive Drugs in Clinical Practice. In: Felipo, V., Grisolía, S. (eds) Advances in Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy. Advances in Experimental Medicine and Biology, vol 420. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5945-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5945-0_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-45598-8

  • Online ISBN: 978-1-4615-5945-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation