Effects of MPTP on Nigrostriatal and Mesolimbic Dopaminergic Systems in Young and Aged Mice

  • Madhu Gupta
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 32)


Parkinson’s disease is a slowly progressive neurodegenerative disorder that seldom occurs in patients below the age of sixty. It is characterized by decreased dopamine in the striatum and a loss of pigmented dopamine neurons in the substantia nigra pars compacta (Forno, 1982; Hornykiewicz, 1982). However, in addition to degeneration of this nigrostriatal system, other monoamine systems also degenerate including the dopaminergic ventral tegmental area, the noradrenergic locus coeruleus system, the cholinergic nucleus basalis system, and the cholinergic dorsal motor nucleus of the vagus (Alvord et al., 1974; Burns et al., 1984; Greenfield and Bosanquet, 1953; Whitehouse et al., 1983). Furthermore, decreased levels of norepinephrine and serotonin and their metabolites in the cerebrospinal fluid have been reported in patients with Parkinson’s disease (Burns et al., 1983; Hornykiewicz, 1982). Normal aging, in the absence of a neurodegenerative disorder, also has been associated with a decline of dopamine levels in the striatum, although the age related decline is more gradual than the decline seen in patients with Parkinson’s disease. Substantia nigra neurons diminish in number with age, leading to decreased synthesis and levels of dopamine in terminal striatal fields (McGeer et al., 1977). Thus, the Parkinson patient appears to have a rapid neurodegenerative process superimposed on top of this age-related decline in the dopaminergic nigrostriatal system.


Substantia Nigra Ventral Tegmental Area Aged Mouse Dopamine Level MPTP Treatment 
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. Forno, L.S., 1982, Pathology of Parkinson’s disease, in: “Movement Disorders,” C.D. Marsden and S. Fahn, ed., Butterworth and Company, London.Google Scholar
  2. Hornykiewicz, O., 1982, Brain neurotarnsmitter changes in Parkinson’s disease, in: “Movement Disorders,” C.D. Marsden and S. Fahn, ed., Butterworth and Company, London.Google Scholar
  3. Alvord, E.C.,Jr., Forno, L.S., Kusske, J.A., Kauffman, R.J., Rhodes, J.S., and Goetowski, C.R., 1974, The pathology of Parkinsonism: A comparison of degenerations in cerebral cortex and brain stem, in: “Second Canadian-American Cinference on Parkinson’s disease,” Advances in Neurology, Vol. 5, F.M. McDowel and A. Barbeau, ed., Raven Press, New York.Google Scholar
  4. Burns, R.S., Markey, S.P., Phillips, J.M., and Chiueh, C.C., 1984, The neurotoxicity of 1-methyl-4-phenyl-l,2,3, 6-tetrahydropyridine in the monkey and man, Can. J. Neurol., 11:166.Google Scholar
  5. Greenfield, J.G. and Bosanquet, F.D., 1953, The brain stem lesions in Parkinsonism, J. Neurol. Neurosurg. Psychiatry, 16:213.PubMedCrossRefGoogle Scholar
  6. Whitehouse, P.J., Hedreen, J.C., White, C.L.III, and Price, D.L., 1983, Basal forebrain neurons in the dementia of Parkinson’s disease, Ann. Neurol., 13:243.PubMedCrossRefGoogle Scholar
  7. Burns, R.S., Chiueh, C.C., Markey, S.P., Ebert, M.H., Jacobowitz, D.M., and Kopin, I.J., 1983, A primate model of Parkinsonism — selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by MPTP, Proc. Natl. Acad. Sci. USA, 80:4546.PubMedCrossRefGoogle Scholar
  8. Carlsson, A. and Winblad, B., 1976, Influence of age and time interval between death and autopsy on dopamine and 3-methoxytyramine levels in human basal ganglia, J. Neural Transm., 38:271.PubMedCrossRefGoogle Scholar
  9. McGeer, P.L., McGeer, E.G., and Suzuki, J.A., 1977, Aging and extrapyramidal function, Arch. Neurol., 34:33.PubMedCrossRefGoogle Scholar
  10. Gupta, M., Feiten, D.L., and Gash, D.M., 1984, MPTP alters central catecholamine neurons in addition to the nigrostriatal system, Brain Res. Bull., 13:737.PubMedCrossRefGoogle Scholar
  11. Gupta, M., Feiten, D.L., and Feiten, S.Y., 1985, MPTP alters monoamine levels in systems other than the nigrostriatal dopaminergic system in mice, in: “MPTP: A neurotoxin producing a Parkinsonian syndrome,” S.P. Markey, N. Castagnoli, JR., A.J. Trevor, and I.J. Kopin, ed., Academic Press, New York.Google Scholar
  12. Hallman, H., Lange, J., Olson, L., Stromberg, I., and Jonsson, G., 1985, Neurochemical and histochemical characterization of neurotoxic effects of MPTP on brain catecholamine neurons in the mouse. J. Neurochem. 44:117.PubMedCrossRefGoogle Scholar
  13. Gupta, M., Gupta, B.K., Thomas, R., Bruemmer, V., Sladek, J.R.,Jr., and Feiten, D.L., 1986, Aged mice are more sensitive to MPTP treatment than young adults, Neuroscience Letts., 70:326.CrossRefGoogle Scholar
  14. Sershan, H., Mason, M.F., Hashim, A., and Lajtha, A., 1985, Effects of MPTP on age-related changes in dopamine turnover and transport function in the mouse striatum. Eur. J. Pharmacol. 113:135.CrossRefGoogle Scholar
  15. Forno, L.S., Langston, J.W., DeLanney, L.E., Irwin, I., and Ricaurte, G.A., 1986, Locus coeruleus lesions and the eosinophilic inclusions in MPTP treated monkeys, Ann. Neurol. 20:449.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Madhu Gupta
    • 1
    • 2
  1. 1.Department of Neurobiology and AnatomyUniversity of Rochester School of MedicineRochesterUSA
  2. 2.Department of PsychiatryLSU School of MedicineShreveportUSA

Personalised recommendations