Brain monoamines in progressive supranuclear palsy — comparison with idiopathic Parkinson’s disease

  • O. Hornykiewicz
  • K. Shannak
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 42)


Like idiopathic Parkinson’s disease (iPD), Progressive Supra-nuclear Palsy (PSP) is characterized, inter alia, by a pronounced non-overlapping loss of dopamine (DA) in caudate, putamen and substantia nigra.

Unlike iPD, in PSP the striatal DA loss is more severe in the caudate than in the putamen; this may contribute to the higher frequency of cognitive deficits in PSP.

In contrast to iPD, in patients with PSP the serotonin (5-HT) levels in the basal ganglia are not significantly reduced, thus resulting in a relative predominance of the inhibitory serotonergic influences on the motor behaviour in these patients.

It is suggested that combination of levodopa with a 5-HT receptor blocker may substantially improve the (poor) responsiveness of patients with PSP to DA substitution therapy.


Basal Ganglion Nucleus Accumbens Caudate Nucleus Progressive Supranuclear Palsy Globus Pallidus 
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. Andén N-E, Grabowska M (1976) Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain. Eur J Pharmacol 39: 275–282.PubMedCrossRefGoogle Scholar
  2. Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental Parkinsonism by lesions of the subthalamic nucleus. Science 249: 1436–1438.PubMedCrossRefGoogle Scholar
  3. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Scitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci 20: 415–455.PubMedCrossRefGoogle Scholar
  4. Bokobza B, Ruberg M, Scatton B, Javoy-Agid F, Agid Y (1984) [3H]Spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 99: 167–175.PubMedCrossRefGoogle Scholar
  5. Borison RL, Pathiraja AP, Diamond BI (1992) Influence of serotonin on dopamin-ergically mediated extrapyramidal side-effects. Mov Disord [Suppl] 7: 55.Google Scholar
  6. Brusa A, Mancardi GL, Bugiani O (1980) Progressive supranuclear palsy 1979: an overview. Ital J Neurol Sci 4: 205–222.Google Scholar
  7. DeLong MR, Georgopoulos AP, Crutcher MD (1983) Cortico-basal ganglia relations and coding of motor performance. Exp Brain Res [Suppl] 7: 29–40.Google Scholar
  8. Divac I, Öberg RGE (1979) Current conceptions of neostriatal functions: history and an evaluation. In: Divac I, Öberg RGE (eds) The neostriatum. Pergamon Press, Oxford, pp 215–230.Google Scholar
  9. Divac I, Rosvold HE, Szwarcbart MK (1967) Behavioural effects of selective ablation of the caudate nucleus. J Comp Physiol Psychol 63: 184–190.PubMedCrossRefGoogle Scholar
  10. Donaldson IMacG, Dolphin AC, Jenner P, Pycock C, Marsden CD (1978) Rotational behaviour produced in rats by ipsilateral electrolytic lesions of the ascending nor-adrenergic bundles. Brain Res 138: 487–509.CrossRefGoogle Scholar
  11. Dray A (1981) Serotonin in the basal ganglia: functions and interactions with other neuronal pathways. J Physiol (Paris) 77: 393–403.Google Scholar
  12. Evarts EV, Kimura M, Wurtz RH, Hikosaka O (1984) Behavioural correlates of activity in basal ganglia neurons. Trends Neurosci 7: 447–453.CrossRefGoogle Scholar
  13. Gibb WRG (1991) Neuropathology of the substantia nigra. Eur Neurol [Suppl 1] 31: 48–59.CrossRefGoogle Scholar
  14. Grenhoff J, Svensson TH (1989) Clonidine modulates dopamine cell firing in rat ventral tegmental area. Eur J Pharmacol 165: 11–18.PubMedCrossRefGoogle Scholar
  15. Hassler R (1938) Zur Pathologie der Paralysis Agitans und des post-enzephalitischen Parkinsonismus. J Psychol Neurol 48: 387–476.Google Scholar
  16. Hornykiewicz O (1976) Neurohumoral interactions and basal ganglia function and dysfunction. In: Yahr MD (ed) The basal ganglia. Raven Press, New York, pp 269–278.Google Scholar
  17. Hornykiewicz O, Kish SJ (1986) Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 45: 19–34.Google Scholar
  18. Hornykiewicz O, Kish SJ, Rajput AH (1990) Neurochemical aspects of Parkinson’s disease and the dementing brain disorders: relation to brain ageing. In: Nagatsu T, Fisher A, Yoshida M (eds) Basic, clinical, and therapeutic aspects of Alzheimer’s and Parkinson’s disease, vol 1. Plenum Press, New York, pp 445–452.CrossRefGoogle Scholar
  19. Jackson JA, Jankovic J, Ford J (1983) Progressive supranuclear palsy: clinical features and response to treatment in 16 patients. Ann Neurol 13: 273–278.PubMedCrossRefGoogle Scholar
  20. Jansen Steur ENH (1993) Increase of Parkinson disability after fluoxetine medication. Neurology 43: 211–213.CrossRefGoogle Scholar
  21. Kish SJ, Chang LJ, Mirchandani L, Shannak K, Hornykiewicz O (1985) Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers. Ann Neurol 18: 530–536.PubMedCrossRefGoogle Scholar
  22. Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. N Engl J Med 318: 876–880.PubMedCrossRefGoogle Scholar
  23. Korsgaard S, Gerlach J, Christensson E (1985) Behavioural aspects of serotonin-dopamine interaction in the monkey. Eur J Pharmacol 118: 245–252.PubMedCrossRefGoogle Scholar
  24. Lategan AJ, Marien MR, Colpaert FC (1990) Effects of locus coeruleus lesions on the release of endogenous dopamine in the rat nucleus accumbens and caudate nucleus as determined by intracerebral microdialysis. Brain Res 523: 134–138.PubMedCrossRefGoogle Scholar
  25. Lloyd KG (1977) Neurotransmitter interactions related to central dopamine neurons. In: Youdim MBH, Lovenberg W, Sharman DE, Lagnado TR (eds) Essays in neurochemistry and neuropharmacology. Wiley, Chichester, pp 131–207.Google Scholar
  26. Maertens de Noordhout A, Delwaide PJ (1986) Open pilot trial of ritanserin in Parkinsonism. Clin Neuropharmacol 9: 480–484.PubMedCrossRefGoogle Scholar
  27. Meco G, Marini S, Lestingi L, Modarelli F, Agnoli A (1986) Efficacy of ritanserin on tremor and abnormal involuntary movements in Parkinson’s disease. Abstract, 15th C.I.N.P. Congress, San Juan, Puerto Rico, p 298.Google Scholar
  28. Mogenson GJ, Yim CY (1981) Electrophysiological and neuropharmacological-behavioural studies of the nucleus accumbens: implications for its role as a limbicmotor interface. In: Chronister RB, Defrance JF (eds) The neurobiology of the nucleus accumbens. Haer Institute for Electrophysiological Research, Brunswick, ME, pp 210–229.Google Scholar
  29. Moore RY, Bloom FE (1978) Central catecholamine neuron systems: anatomy and physiology of the dopamine systems. Ann Rev Neurosci 1: 129–169.PubMedCrossRefGoogle Scholar
  30. Narabayashi H (1993) Three types of akinesia in the progressive course of Parkinson’s disease. Adv Neurol 60: 18–24.PubMedGoogle Scholar
  31. Nyberg P, Nordberg A, Wester P, Winblad B (1983) Dopaminergic deficiency is more pronounced in putamen than in nucleus caudatus in Parkinson’s disease. Neurochem Pathol 1: 193–202.CrossRefGoogle Scholar
  32. Owen AM, Beksinska M, James M, Leigh PN, Summers BA, Marsden CD, Quinn NP, Sahakian BJ, Robbins TW (1993) Visuo-spatial memory deficits at different stages of Parkinson’s disease. Neuropsychologia (in press).Google Scholar
  33. Ruberg M, Javoy-Agid F, Hirsch E, Scatton B, LHeureux R, Hauw JJ, Duyckaerts C, Gray F, Morel-Maroger A, Rascol A, Serdaru M, Agid Y (1985) Dopaminergic and cholinergic lesions in progressive supranuclear palsy. Ann Neurol 18: 523–529.PubMedCrossRefGoogle Scholar
  34. Steele JC, Richardson JC, Olszewski J (1964) Progressive supranuclear palsy. Arch Neurol 10: 333–359.PubMedCrossRefGoogle Scholar
  35. Ugedo L, Grenhoff J, Svensson TH (1989) Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition. Psycho-pharmacology 98: 45–50.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1994

Authors and Affiliations

  • O. Hornykiewicz
    • 1
  • K. Shannak
    • 2
  1. 1.Institute of Biochemical PharmacologyUniversity of ViennaWienAustria
  2. 2.Clarke Institute of PsychiatryUniversity of TorontoTorontoCanada

Personalised recommendations