Cerebral serotonin in viral encephalitis

  • L. Lima
  • B. Drujan
  • R. Walder
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 29)


In order to evaluate central serotonergic function during viral encephalitis biochemical, behavioural and immunohistofluorescence studies were carried out. Mice were inoculated with the moderate virulent strain of Venezuelan equine encephalomyelitis virus, Pixuna. Signs of encephalitis were observed in 50–60% of infected animals. Levels of serotonin and 5-hydroxyindolacetic acid, and the ratio of the indolamine and its metabolite in raphe and cortex did not change with respect to sham-inoculated mice. A differential decrease in turnover rate by pharmacological methods, such as pargyline, p-chlorophenylalanine and probenecid administration, was observed in raphe and cortex. The ratio serotonin turnover rate/steady state concentration of serotonin was only decreased in the raphe of sick animals. The response to 5-methoxy-N, N-dimethyltrypt-amine was greater in infected animals. The duration of immobility in the swim test was shorter in the infected group. A greater number of viral antigen particles was localized in raphe and periraphe areas than in cortex, brain stem or striatum. The results suggest a serotonin presynaptic deficit, a postsynaptic hyperreactivity of serotonin system, and a region-selective distribution of the virus.


Viral Encephalitis Venezuelan Equine Encephalomyelitis Virus Sick Animal BioI Psychiatry Monoamine Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aghajanian GK, Kubar MJ, Roth RH (1973) Serotoning containing neuronal perikarya and terminals: differential effects of p-chlorophenylalanine. Brain Res 54: 85–101.PubMedCrossRefGoogle Scholar
  2. Allen D, Fudenberg HH, Allen RE (1987) Affective disorder and viral infections. Arch Gen Psychiatry 44: 760.PubMedCrossRefGoogle Scholar
  3. Bonilla E, Ryder E, Ryder S (1980) GAB A metabolism in Venezuelan equine encephalo-myelitis virus infection. Neurochem Res 5: 209–215.PubMedCrossRefGoogle Scholar
  4. Bonilla E, Hernández H, Salazar M, Rangel P (1982) Effect of Venezuelan equine enceph-alomyelitis virus infection on brain choline acetyltransferase and acetylcholinesterase activities. Brain Res 253: 330–333.PubMedCrossRefGoogle Scholar
  5. Bonilla E, Salazar M, Estévez J, Hernández H, Rangel P (1984) (3H) Spiroperidol binding decreases in brains of rats infected with Venezuelan equine encephalomyelitis virus. Experientia 40: 868–869.PubMedCrossRefGoogle Scholar
  6. Bonilla E, Prasad AL, Estévez J, Hernández H, Arrieta A (1986) Free amino acids in the striatum of mice infected with Venezuelan equine encephalomyelitis virus. Exp Neurol 93: 434–439.PubMedCrossRefGoogle Scholar
  7. Corne SJ, Pickering RE, Warner BT (1963) A method of assessing the effects of drugs on the central actions of 5-hydroxytryptamine. Br J Pharmacol 20: 106–210.Google Scholar
  8. Crow TJ, Owens O, Fernier J, MacMillan J, Caroy R, Tyrell D (1979) Characteristic of patients with schizophrenia or neurological disorder and virus-like agent. Lancet i: 842–844.CrossRefGoogle Scholar
  9. Crow TJ (1983) Is schizophrenia an infectious disease? Lancet i: 173–175.CrossRefGoogle Scholar
  10. Crow TJ (1987) Psychosis as a continuum and the virogene concept. Br Med Bull 43: 755–767.Google Scholar
  11. Damasio AR, Vanhoese GW (1985) The limbic system and the localization of herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry 48: 297–301.PubMedCrossRefGoogle Scholar
  12. Delamonte SM (1985) Selective vulnerability of particular central neurons system regions to east equine encephalitis virus infection in humans. J Neurophatol Exp Neurol 44: 358–361.CrossRefGoogle Scholar
  13. Delsedime M, Cantello R, Durelli L, Gilli M, Giordana TM (1984) A syndrome resembling limbic encephalitis, associated with branchial carcinoma, but without neuropathological abnormality: a case report. J Neurol 213: 165–166.CrossRefGoogle Scholar
  14. Fields BN, Weiner HL (1982) Mechanism of viral injury to the nervous system. In: Sears TA (ed) Neuronal-glial cell inter-relationships, pp 217-228.Google Scholar
  15. Fishman P, Gass J, Swoveland P (1985) Infection of the basal ganglia by a murine coron-avirus. Science 229: 877–879.PubMedCrossRefGoogle Scholar
  16. Gerson SC, Baldessarini RJ (1980) Motor effects of serotonin in the central nervious system. Life Sci 27: 1435–1451.PubMedCrossRefGoogle Scholar
  17. Gibson CJ, Diekel SM, Young SN, Binik TM (1982) Behavioural and biochemical effects of tryptophan, tyrosine and phenylalanine and central serotonin neurons. Pol J Pharmacol Pharm 25: 29–39.Google Scholar
  18. Glowinski J, Iversen L (1966) Regional studies of catecholamines in the rat brain. I. Disposition of 3H-Norepinerphrine, 3H-Dopamine and 3H-DOPA in various regions of the brain. J Neurochem 13: 655–669.PubMedCrossRefGoogle Scholar
  19. Grahame-Smith DG (1971) Inhibitory effect of chlorpromazine on syndrome of hyper-reactivity produced by L-tryptophan or 5-methoxy-N,N-dimethyltryptamine in rats treated with monoaminoxidase inhibitor. Br J Pharmacol 43: 856–864.PubMedGoogle Scholar
  20. Jacobs BL (1976) An animal behavior model for studying central serotoninergic synapses. Life Sci 19: 777–786.PubMedCrossRefGoogle Scholar
  21. Johnson RT (1982) Viral infections of the nervous system. Raven Press, New York.Google Scholar
  22. Kaufman CA, Weinberger DR, Yolken RH, Torrey EF, Potkin SG (1983) Viruses and schizophrenia. Lancet ii: 1136–1137.CrossRefGoogle Scholar
  23. Koehler K, Guth W (1979) The mimicking of mania in bening herpes simplex encephalitis. Biol Psychiatry 14: 405–408.PubMedGoogle Scholar
  24. Kristensson K (1982) In: Weiss DG, Gorio A (eds) Axoplasmic transport in physiology and pathology. Springer, Berlin Heidelberg New York, pp 153–159.Google Scholar
  25. Leon C, Jaramillo R, Martínez S, Fernández T, Téllez H, Lasso B, Guzmán R (1975) Sequelae of Venezuelan equine encephalitis in humans: a four year follow-up. Int J Epidemiol 4: 131–140.PubMedCrossRefGoogle Scholar
  26. Levine S, Bonilla E, Ryder S, Salazar M, Rangel P (1981) Tyrosine hydroxilanse activity in Venezuelan equine encephalomyelitis virus infection. Neurochem Res 6: 691–697.PubMedCrossRefGoogle Scholar
  27. Lima L, Díaz-Borges JM, Walder R (1983) Influence of Venezuelan equine encephalomyelitis virus on catecholamine metabolisms in mouse CNS: early changes in turnover rates and content. J Neurosci Res 10: 61–71.PubMedCrossRefGoogle Scholar
  28. Lima L, Walder R, Obregón F, Drujan B (1987) Serotonin turnover rate in raphe and cortex of mice infected with Venezuelan equine encephalomyelitis virus. J Neurosci Res 17: 428–434.PubMedCrossRefGoogle Scholar
  29. Lima L, Ayala C, Walder R, Drujan B (1988) Behavioural effects produced in mice infected with Venezuelan equine encephalomyelitis virus. Physiol Behav 43: 281–286.PubMedCrossRefGoogle Scholar
  30. Lipkin WI, Tyler KL, Waksman BH (1988) Viruses, the immune system and central nervous system disease. Trends Neurosci 11: 43–45.PubMedCrossRefGoogle Scholar
  31. Lycke E, Ross BE (1969) Aggression in mice associated with changes in the monoamine metabolism of the brain. Experientia 25: 951–953.PubMedCrossRefGoogle Scholar
  32. Lycke E, Ross BE (1970) The monoamine metabolism in viral encephalitis of the mouse. I. Virological and biochemical results. Brain Res 23: 235–256.PubMedCrossRefGoogle Scholar
  33. Lycke E, Ross BE (1972) The monoamine metabolism in viral encephalitis of mouse. II. Turnover of monoamine in mice infected with herpes simplex virus. Brain Res 44: 603–613.PubMedCrossRefGoogle Scholar
  34. Maratos-Flier E, Kahn CR, Spriggs DR, Fields BN (1983) Specific plasma membrane receptors for reovirus on rat pituitary cells in culture. J Clin Invest 72: 617–621.PubMedCrossRefGoogle Scholar
  35. Maurizi CP (1984) Influenza and schizophrenia: a possible connection with the substantia nigra. Med Hypotheses 15: 163–167.PubMedCrossRefGoogle Scholar
  36. Maurizi CP (1985a) Influenza and mania, a possible connection with locus coeruleus. South Med J 78: 207–209.PubMedCrossRefGoogle Scholar
  37. Maurizi CP (1985b) Raphe nucleus encephalopathy (myalgic encephalomyelitis, epidemic neuromyastenia). Med Hypotheses 16: 351–354.PubMedCrossRefGoogle Scholar
  38. Meek JL, Lofstrandh S (1976) Tryptophan hydroxylase in discrete brain nuclei. Comparison of activity in vitro and in vivo. Eur J Pharmacol 37: 377–380.PubMedCrossRefGoogle Scholar
  39. Meijer A, Zakay-Rones Z, Morag A (1988) Post-influenzal psychiatric disorder in adolescents. Acta Psychiatr Scand 78: 176–181.PubMedCrossRefGoogle Scholar
  40. Miyasaki K, Takayashi T (1977) Parkinsonism following encephalitis of unknown etiology. J Neuropathol Exp Neurol 36: 1–8.PubMedCrossRefGoogle Scholar
  41. Monath TP, McLean RG, Cropp CB, Parham GL, Lazuick JS, Calisher CH (1981) Diagnosis of eastern equine encephalomyelitis by immunofluorescent staining of brain tissue. Am J Vet Res 42: 1418–1421.PubMedGoogle Scholar
  42. Porsolt RD, Jalfre M (1977) Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229: 327–336.PubMedGoogle Scholar
  43. Rhodes RH, Novak R, Beattie JF, West HM, Whetsell WO (1984) Immunoperoxidase demonstration of herpes simplex virus Type-I in the brain of a psychotic patient without history of encephalitis. Clin Neurol 3: 59–67.Google Scholar
  44. Sharpe AH, Fields BN (1985) Pathogenesis of viral infections: basic concepts derived from the reovirus model. New Eng J Med 312: 486–497.PubMedCrossRefGoogle Scholar
  45. Simantov R, Oster-Granite ML, Herndon RM, Snyder SH (1976) Gamma-aminobutyric acid (GABA) receptor binding selectively depleted by viral induced granule cell loss in hamster cerebellum. Brain Res 105: 365–371.PubMedCrossRefGoogle Scholar
  46. Sokal R, Rohlf F (1979) Biometria. Blume Ediciones, Madrid.Google Scholar
  47. Soubrié P (1986) Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 9: 319–364.CrossRefGoogle Scholar
  48. Torrey EF (1988) Stalking the schizovirus. Schizophr Bull 14: 223–229.PubMedGoogle Scholar
  49. Tsiang H, Gourmelon P, Briet D, Court L (1988) Sleep stace and EEG alterations in rabies. Neurochem Int 13: 65.Google Scholar
  50. Tyler KL (1986) Localized infection of the central nervous system. Curr Ther Infect Dis 1: 216–225.Google Scholar
  51. Tyrrel DA, Parry RP, Crow TJ, Johnstone E, Ferrier IN (1979) Possible virus in schizophrenia and some neurological disorders. Lancet ii: 839–841.CrossRefGoogle Scholar
  52. van Kämmen DP (1987) 5-HT, a neurotransmitter for all seasons? Biol Psychiatry 22: 1–3.PubMedCrossRefGoogle Scholar
  53. von Economo C (1931) Encephalitis lethargic: its sequelae and treatment. Oxford University Press, London.Google Scholar
  54. Walder R, Bradish C (1979) Multi-factorial specifications of virus-host interactions: studies with strains of Venezuelan equine encephalomyelitis virus in mice. J Gen Virol 44: 373–382.PubMedCrossRefGoogle Scholar
  55. Ziegler RJ, Trachte G, Stauffer E (1988) Persistent virus effects on neuronal electrophy-siology and prostaglandin metabolism. Neurochem Int 13: 65.Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • L. Lima
    • 1
    • 3
  • B. Drujan
    • 1
  • R. Walder
    • 2
  1. 1.Laboratorios de NeuroquímicaInstituto Venezolano de Investigaciones Científicas (IVIC)CaracasVenezuela
  2. 2.Virologia AnimalInstituto Venezolano de Investigaciones Científicas (IVIC)CaracasVenezuela
  3. 3.Laboratorio de NeuroquímicaInstituto Venezolano de Investigaciones Cientificas (IVIC)CaracasVenezuela

Personalised recommendations