Age-Dependent Effects of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in the Rat

  • Klaus W. Lange
Part of the Advances in Behavioral Biology book series (ABBI, volume 38A)


1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a Parkinsonian syndrome in humans and monkeys which is accompanied by degeneration of dopamine containing neurones in the substantia nigra pars compacta (SNC) and extensive loss of dopamine in the striatum (for review see Langston, 1987). Rats are much less sensitive to the neurotoxicity of MPTP than primates. Systemic administration of MPTP to rats did not produce neurotoxic effects (Chiueh et al., 1984) and intranigral administration failed to induce lasting damage to the SNC neurones (Chiueh et al., 1984; Bradbury et al., 1986) or lasting behavioural effects (Welzl and Lange, 1986). The neurotoxicity of MPTP seems to be age-dependent. It has been demonstrated that old mice suffer more extensive neuronal damage in the SNC than younger animals in response to MPTP administration (Gupta et al., 1986). The present experiment studied the age-dependent effects of unilateral intranigral administration of MPTP in the rat.


Nigrostriatal Dopamine MPTP Administration MPTP Injection Striatal Dopamine Depletion Lasting Damage 
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. Benedetti, M.S., and Keane, P.E., 1980, Differential changes in monoamine oxidase A and B activity in the aging rat brain, J. Neurochem., 35: 1026.PubMedCrossRefGoogle Scholar
  2. Bradbury, A.J., Costall, B., Domeney, A.M., Jenner, P., Kelly, M.E., Marsden, C.D., and Naylor, R.J., 1986, 1-Methyl-4-phenylpyridine is neurotoxic to the nigrostriatal dopamine pathway, Nature, 319: 56.PubMedCrossRefGoogle Scholar
  3. Chiueh, C.C., Markey, S.P., Burns, R.S., Johannessen, J.N., Pert, A., and Kopin, I.J., 1984, Neurochemical and behavioral effects of systemic and intranigral administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the rat, Eur. J. Pharmacol., 100: 189.PubMedCrossRefGoogle Scholar
  4. Creese, I., Burt, D.R., and Snyder, S.H., 1977, Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity, Science, 197: 596.PubMedCrossRefGoogle Scholar
  5. Gupta, M., Gupta, B.K., Thomas, R., Bruemmer, V., Sladek Jr., J.R., and Felten, D.L., 1986, Aged mice are more sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment than young adults, Neurosci. Lett., 70: 326.PubMedCrossRefGoogle Scholar
  6. Irwin, I., Ricaurte, G.A., DeLanney, L.E., and Langston, J.W., 1988, The sensitivity of nigrostriatal dopamine neurons to MPP+ does not increase with age, Neurosci. Lett., 87: 51.PubMedCrossRefGoogle Scholar
  7. Jarvis, M.F., and Wagner, G.C., 1985, Age-dependent effects of 1-methyl-4-phenyl1,2,5,6-tetrahydropyridine ( MPTP ), Neuropharmacology, 24: 581.PubMedCrossRefGoogle Scholar
  8. König, J.F.R., and Klippel, R.A., 1963, “The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem”, Williams and Wilkins, Baltimore.Google Scholar
  9. Lange, K.W., 1989, Circling behavior in old rats after unilateral intranigral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP ), Life Sci., 45: 1709.PubMedCrossRefGoogle Scholar
  10. Langston, J.W., 1987, MPTP: The promise of a new neurotoxin, in: “Movement Disorders 2”, C.D. Marsden and S. Fahn, eds., Butterworths, London.Google Scholar
  11. Langston, J.W., Irwin, I., and DeLanney, L.E., 1987, The biotransformation of MPTP and disposition of MPP+: The effects of aging, Life Sci., 40: 749.PubMedCrossRefGoogle Scholar
  12. Ricaurte, G.A., Irwin, I., Forno, L.S., DeLanney, L.E., Langston, E.B., and Langston, J.W., 1987, Aging and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of dopaminergic neurons in the substantia nigra, Brain Res., 403: 43.PubMedCrossRefGoogle Scholar
  13. Ungerstedt, U., 1971, Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of nigro-striatal dopamine system, Acta Physiol. Scand. Suppl., 367: 69.PubMedGoogle Scholar
  14. Walsh, S.L., and Wagner, G.C., 1989, Age-dependent effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Correlation with monoamine oxidase-B, Synapse, 3: 308.PubMedCrossRefGoogle Scholar
  15. Welzl, H., and Lange, K.W., 1986, Unilateral intranigral injection of MPTP in the rat induces contraversive turning, Eur. J. Pharmacol., 132: 295.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Klaus W. Lange
    • 1
    • 2
  1. 1.University Department of Neurology and Parkinson’s Disease Society Research CentreInstitute of Psychiatry and King’s College School of MedicineLondonUK
  2. 2.Laboratory of Psychobiology Institute of PsychologyUniversity of DüsseldorfDüsseldorfGermany

Personalised recommendations