Skip to main content
PMC home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2003 Mar 17;35(2):355–363. doi: 10.1016/0306-4522(90)90089-M

Behavioural deficits and serotonin depletion in adult rats after transient infant nasal viral infection

AK Mohammed *, O Magnusson *,†, J Maehlen ‡, F Fonnum §, E Norrby ∥, M Schultzberg , K Kristensson ¶,**
PMCID: PMC7131220  PMID: 1696362

Abstract

Dysfunction of subcortical serotoninergic neurons has been implicated in some behaviour disturbances. The serotoninergic neurons in the dorsal and median raphe project widely in the brain. They innervate the olfactory bulbs and can be targets for exogenous agents attacking the olfactory epithelium and bulbs. We report here an injury to the serotoninergic neurons after intranasal infection in 12-day-old rats with a temperature-sensitive mutant of vesicular stomatitis virus. The brain infection was focal and transient. Viral antigens could no longer be detected 13–15 days after infection. In spite of this the animals, as adults, had a severe serotonin depletion in the cerebral cortex and hippocampus, and showed abnormal locomotor and explorative behaviour as well as learning deficits. The neocortex was histologically intact and parameters related to other neurotransmitters such as dopamine, noradrenaline, GABA and acetylcholine showed no marked changes.

A relatively selective damage to serotoninergic nuclei as a result of virus neuroinvasion through a natural portal of entry, may constitute a new pathogenetic mechanism for cortical dysfunction and behavioural deficits.

Keywords: ChAT, choline acetyltransferase; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; GAD, glutamate decarboxylase; 5-HIAA, 5-hydroxyindole acetic acid; 5-HT, 5-hydroxytryptamine; HVA, homovanillic acid; NA, noradrenaline; p.i., post infection; VSV, vesicular stomatitis virus

References

  • 1.Aghajanian G.K., Spouse J.S., Rasmussen K. Physiology of the midbrain serotonin system. In: Meltzer H.Y., Coyl J.T., Bunne W.E., Kopi I.J., Davis K.L., Schuste C.R., Shade R.I., Simpso G.M., editors. Psychopharmacology, The Third Generation of Progress. Raven Press; New York: 1987. pp. 141–150. [Google Scholar]
  • 2.Ahlenius S., Hillegaart V. Involvement of extrapyramidal motor mechanisms in the suppression of locomotor activity by antipsychotic drugs: a comparison between the effects produced by pre- and post-synaptic inhibition of dopaminergic neurotransmission. Pharmac. Biochem. Behav. 1986;24:1409–1415. doi: 10.1016/0091-3057(86)90203-0. [DOI] [PubMed] [Google Scholar]
  • 3.Campbell B.A., Ballantine P., Lynch G.S. Hippocampal control of behavioral arousal: duration of lesion effects and possible interactions with recovery after frontal cortical damage. Expl Neurol. 1971;33:159–170. doi: 10.1016/0014-4886(71)90110-5. [DOI] [PubMed] [Google Scholar]
  • 4.Campbell B.A., Lytle L., Fibiger H.C. Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science. 1969;166:635–637. doi: 10.1126/science.166.3905.635. [DOI] [PubMed] [Google Scholar]
  • 5.Coyle J.T. In: Diseases of the Nervous System. Asbury A.K., McKhann G.M., McDonald W.I., editors. W. B. Saunders; Philadelphia: 1986. pp. 880–889. [Google Scholar]
  • 6.Descarries L., Doucet G., Lemay B., Séguéla P., Watkins K.C. Structural basis of cortical monoamine function. In: Avoli M., Dykes R.W., Reader T.A., Gloor P., editors. Neurotransmitters and Cortical Function. Plenum Press; New York: 1988. pp. 321–332. [Google Scholar]
  • 7.Fibiger H.C., Campbell B.A. The effect of parachlorophenylalanine on spontaneous locomotor activity in the rat. Neuropharmacology. 1971;10:25–32. doi: 10.1016/0028-3908(71)90005-0. [DOI] [PubMed] [Google Scholar]
  • 8.Fishman P.S., Gass J.S., Swoveland P.T., Lavi E., Highkin M.K., Weiss S.R. Infection of the basal ganglia by a murin corona virus. Science. 1985;229:877–879. doi: 10.1126/science.2992088. [DOI] [PubMed] [Google Scholar]
  • 9.Fonnum F. A rapid radiochemical method for the determination of choline acetyltransferase. J. Neurochem. 1975;24:407–409. doi: 10.1111/j.1471-4159.1975.tb11895.x. [DOI] [PubMed] [Google Scholar]
  • 10.Fonnum F., Storm-Mathisen J., Walberg F. Glutamate decarboxylase in inhibitory neurons. A study of the enzyme in Purkinje cell axons and boutons in the cat. Brain Res. 1970;20:259–275. doi: 10.1016/0006-8993(70)90293-3. [DOI] [PubMed] [Google Scholar]
  • 11.Hernàndez-Rodriguez J., Chagoya G. Brain serotonin synthesis and Na+, K+-ATPase activity are increased postnatally after prenatal administration of l-tryptophan. Devl Brain Res. 1986;25:221–226. doi: 10.1016/s0006-8993(86)80230-x. [DOI] [PubMed] [Google Scholar]
  • 12.Hole K., Fuxe K., Jonsson G. Behavioral effects of 5,7-dihydroxytryptamine lesions of ascending 5-hydroxytryptamine pathways. Brain Res. 1976;107:385–399. doi: 10.1016/0006-8993(76)90235-3. [DOI] [PubMed] [Google Scholar]
  • 13.Hotchin J., Seegal R. Virus-induced behavioral alteration of mice. Science. 1976;196:671–674. doi: 10.1126/science.854742. [DOI] [PubMed] [Google Scholar]
  • 14.Johnson R.T. Raven Press; New York: 1982. Viral Infections of the Nervous System. [Google Scholar]
  • 15.Köhler C., Lorens S.A. Open field activity and avoidance behavior following serotonin depletion: a comparison of the effects of para-chlorophenylalanine and electrolytic midbrain raphe lesions. Pharmac. Biochem. Behav. 1978;8:223–233. doi: 10.1016/0091-3057(78)90309-x. [DOI] [PubMed] [Google Scholar]
  • 16.Lees A.J., Fernando J.C.R., Curzon G. Serotonergic involvement in behavioural responses to amphetamine at high dosage. Neuropharmacology. 1979;18:153–158. doi: 10.1016/0028-3908(79)90055-8. [DOI] [PubMed] [Google Scholar]
  • 17.Lima L., Ayala C., Walder R., Drujan B. Behavioural effects produced in mice infected with Venezuelan equine encephalomyelitis virus. Physiol. Behav. 1988;43:281–286. doi: 10.1016/0031-9384(88)90188-6. [DOI] [PubMed] [Google Scholar]
  • 18.Lucot J.B., Seiden L.S. Effects of neonatal administration of 5,7-dihydroxytryptamine on locomotor activity. Psychopharmacology. 1982;77:114–116. doi: 10.1007/BF00431931. [DOI] [PubMed] [Google Scholar]
  • 19.Lucot J.B., Seiden L.S. Effects of serotonergic agonists and antagonists on the locomotor activity of neonatal rats. Pharmac. Biochem. Behav. 1986;24:537–541. doi: 10.1016/0091-3057(86)90554-x. [DOI] [PubMed] [Google Scholar]
  • 20.Lundh B., Kristensson K., Norrby E. Selective infections of olfactory epithelium by vesicular stomatitis and Sendai viruses. Neuropath. appl. Neurobiol. 1987;13:111–122. doi: 10.1111/j.1365-2990.1987.tb00175.x. [DOI] [PubMed] [Google Scholar]
  • 21.Lundh B., Löve A., Kristensson K., Norrby E. Non-lethal infection of aminergic reticular core neurons: age-dependent spread of ts mutant vesicular stomatitis virus from the nose. J. Neuropathol. exp. Neurol. 1988;47:497–506. doi: 10.1097/00005072-198809000-00001. [DOI] [PubMed] [Google Scholar]
  • 22.Lycke E., Modigh K., Roos B.-E. Aggression in mice associated with changes in the monoamine metabolism of the brain. Experientia. 1969;52:951–953. doi: 10.1007/BF01898084. [DOI] [PubMed] [Google Scholar]
  • 23.Lynch G.S., Ballantine P., Campbell B.A. Potentiation of behavioral arousal after cortical damage and subsequent recovery. Expl Neurol. 1969;23:195–206. doi: 10.1016/0014-4886(69)90056-9. [DOI] [PubMed] [Google Scholar]
  • 24.Mabry P.D., Campbell B.A. Ontogeny of serotonergic inhibition of behavioral arousal in the rat. J. comp, physiol. Psychol. 1974;86:193–201. doi: 10.1037/h0035946. [DOI] [PubMed] [Google Scholar]
  • 25.Magnusson O., Nilsson L.B., Westerlund D. Simultaneous determination of dopamine, DOPAC and homovanillic acid. Direct injection of supernatants from brain tissue homogenates in a liquid chromatographyelectrochemical detection system. J. Chromat. 1980;221:237–247. [PubMed] [Google Scholar]
  • 26.Mohammed A.K., Jonsson G., Sundström E., Minor B.G., Söderberg U., Archer T. Selective attention and place navigation in rats treated prenatally with methylazoxymethanol. Devl Brain Res. 1986;30:145–155. doi: 10.1016/s0006-8993(86)80194-9. [DOI] [PubMed] [Google Scholar]
  • 27.Morris R.G.M. Development of a water maze procedure for studying spatial learning in the rat. J. Neurosci. Meth. 1984;11:47–60. doi: 10.1016/0165-0270(84)90007-4. [DOI] [PubMed] [Google Scholar]
  • Morris R.G.M., Garrud P., Rawlins J.N.P., O'Keefe J. Place navigation is impaired in rats with hippocampal lesions. Nature. 1982;297:681–683. doi: 10.1038/297681a0. [DOI] [PubMed] [Google Scholar]
  • 28.Ögren S.O. Evidence for a role of brain serotonergic neurotransmission in avoidance learning. Acta physiol. scand. 1985;125(Suppl. 544):1–71. [PubMed] [Google Scholar]
  • 29.Ögren S.O., Johansson C., Magnusson O. Forebrain serotonergic involvement in avoidance learning. Neurosci. Lett. 1985;58:305–309. doi: 10.1016/0304-3940(85)90071-0. [DOI] [PubMed] [Google Scholar]
  • 30.Olson L., Seiger A.˚. Early prenatal ontogeny of central monoamine neurons in the rat: fluorescence histochemical observations. Z. Anat. Entw. Gesch. 1972;137:301–316. doi: 10.1007/BF00519099. [DOI] [PubMed] [Google Scholar]
  • 31.Park D.H., Snyder D.W., Joh T.H. Postnatal developmental changes of tryptophan hydroxylase activity in serotonergic cell bodies and terminals of rat brain. Brain Res. 1986:183–185. doi: 10.1016/0006-8993(86)90303-3. [DOI] [PubMed] [Google Scholar]
  • 32.Preble O.T., Costello L.E., Huang D.D., Barmada M.A. Neurovirulent mutant of vesicular stomatitis virus with an altered target cell tropism in vivo. Infect. Immun. 1980;29:744–757. doi: 10.1128/iai.29.2.744-757.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Rabinowitz S.G., Dal Canto M.C., Johnson T.C. Comparison of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus. Infect. Immun. 1976;13:1242–1249. doi: 10.1128/iai.13.4.1242-1249.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Shipley M.T. Transport of molecules from nose to brain: transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat-germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res. Bull. 1985;12:129–142. doi: 10.1016/0361-9230(85)90129-7. [DOI] [PubMed] [Google Scholar]
  • 35.Shipley M.T., Adamek G.D. The connections of the mouse olfactory bulb: a study using orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Brain Res. Bull. 1984;12:669–688. doi: 10.1016/0361-9230(84)90148-5. [DOI] [PubMed] [Google Scholar]
  • 36.Talamo B.R., Rudel R.A., Kosik K.S., Lee V.M.-Y., Neff S., Adelman L., Kauer J. Pathological changes in olfactory neuron in patients with Alzheimer's disease. Nature. 1989;337:736–739. doi: 10.1038/337736a0. [DOI] [PubMed] [Google Scholar]
  • 37.Torvik A., Meen D. Distribution of the brainstem lesions in postencephalic Parkinsonism. Acta neurol. scand. 1966;42:415–425. doi: 10.1111/j.1600-0404.1966.tb01193.x. [DOI] [PubMed] [Google Scholar]
  • 38.Von Economo C. Oxford University Press; London: 1931. Encephalitis Lethargica: its Sequelae and Treatment. [Google Scholar]
  • 39.Warbritton J.D., Stewart R.M., Baldessarini R.J. Decreased locomotor activity and attenuation of amphetamine hyperactivity with intraventricular infusion of serotonin in the rat. Brain Res. 1978;143:373–382. doi: 10.1016/0006-8993(78)90578-4. [DOI] [PubMed] [Google Scholar]
  • 40.Winer B.J. 2nd edn. McGraw Hill; New York: 1971. Statistical Principles in Experimental Design. [Google Scholar]
  • 41.Young J.G., Halperin J.M., Leven L.I., Shaywitz B.A., Cohen D.J. Developmental neuropharmacology: clinical and neurochemical perspectives on the regulation of attention, learning and movement. In: Iversen L.L., Iverse S.D., Snyder S.H., editors. Plenum Press; New York: 1987. pp. 59–121. (Handbook of Psychopharmacology). [Google Scholar]

Articles from Neuroscience are provided here courtesy of Elsevier

RESOURCES