The Clinical Evaluation of Drug Therapy in Parkinsonism and Models of Dysfunction of Brain Dopamine Systems in Animals

A Review
  • J. R. Bianchine
  • R. D. Schwartz
  • C. W. RichardIII


The observation by Ehringer and Hornykiewicz (1960) that patients who had died with Parkinson’s disease showed cellular degeneration of basal ganglia structures and a deficiency of dopamine (DA) within this area was a key link in the concept that a deficiency in a specific substance was intimately involved in the pathogenesis of a neurological disorder. The efficacy of levodopa treatment in Parkinson’s disease obviously reinforced this idea. At about the same time as these discoveries, both biochemical and histological techniques became available for researchers to examine brain catecholamine systems that appeared to be involved in neurological illnesses (Carlsson, 1959; Dahlström and Fuxe, 1964).


Tardive Dyskinesia Squirrel Monkey Locomotor Behavior Parkinsonian Patient Dopaminergic Drug 
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  1. Alba, A., Trainor, Frieda, S., Ritter, W., and Dacso, M. M., 1968, A clinical disability rating for Parkinson patients, J. Chron. Dis. 21: 507–522.PubMedCrossRefGoogle Scholar
  2. Arbuthnott, G. W., and Ungerstedt, U., 1975, Turning behavior induced by electrical stimulation of the nigro-neostiratal system of the rat, Exp. Neurol. 47: 162–172.PubMedCrossRefGoogle Scholar
  3. Arnfred, T., and Randrup, A., 1968, Cholinergic mechanisms in brain inhibiting amphetamine-induced stereotyped behavior, Acta. Pharmacol. Toxicol. 26: 384–394.CrossRefGoogle Scholar
  4. Baldessarini, R. J., and Tarsy, D., 1980, Dopamine and the pathophysiology of dyskinesias induced by antipsychotic drugs, Ann. Rev. Neurosci. 3: 23–41.PubMedCrossRefGoogle Scholar
  5. Bianchine, J. R., 1974, Evaluation of drug therapy in Parkinson’s disease, in: Principles and Techniques of Human Research and Therapeutics: Psychopharmacological Agents, Vol. 8 ( F. G. McMahon, ed.), pp. 171–179, Futura Publishing Company, New York.Google Scholar
  6. Bianchine, J. R., 1980, Drugs for Parkinson’s disease; Centrally acting muscle relaxants, in: The Pharmacologic Basis of Therapeutics ( A. G. Gilman, L. S. Goodman, and A. Gilman, eds.), pp. 475–493, Macmillan, New York.Google Scholar
  7. Bianchine, J. R., Calimlim, L. R., Morgan, J. P., Dujovne, C. A., and Lasagna, I.., 1971, Metabolism and absorption of L-3,4 dihydroxyphenylalanine in patients with Parkinson’s disease, Ann. NYAcad. Sci. 179: 126–140.Google Scholar
  8. Bianchine, J. R., Shaw, G. M., Greenwald, J. E., and Dandalides, S. M., 1978, Clinical aspects of dopamine agonists and antagonists, Fed. Proc. 37:2434–2439.Google Scholar
  9. Boman, K., and Meurman, T., 1970, Investigation on the effect of some drugs on the Parkinsonian rigidity, Acta. Neurol. Scand. 46: 71–84.PubMedCrossRefGoogle Scholar
  10. Canter, G. J., DeLatorre, R., and Mier, M., 1961, A method for evaluating disability in patients with Parkinson’s disease, J. Nerv. Ment. Dis. 133: 143–147.PubMedCrossRefGoogle Scholar
  11. Carlsson, A., 1959, The occurance, distribution, and physiological role of catecholamines in the nervous system, Pharmacol. Rev. 11: 490–493.PubMedGoogle Scholar
  12. Casey, D. E., Gerlach, J., and Christensson, E., 1980, Dopamine, acetylcholine, and GABA effects in acute dystonia in primates, Psychopharmacology 70: 83–87.PubMedCrossRefGoogle Scholar
  13. Costall, B., and Naylor, R. J., 1973, The role of telencephalic dopaminergic systems in the mediation of apomorphine-stereotyped behaviour, Eur. J. Pharmacol. 24: 8–24.PubMedCrossRefGoogle Scholar
  14. Costall, B., and Naylor, R. J., 1974, Specific asymmetric behavior induced by the direct chemical stimulation of neostriatal dopaminergic mechanisms, Naunyn-Schmeideberg’s Arch. Pharmacol. 285: 83–98.CrossRefGoogle Scholar
  15. Costall, B., Naylor, R. J., and Olley, J. E., 1972, Catalepsy and circling behaviour after intracerebral injections of neuroleptic, cholinergic and anticholinergic agents into the caudate-putamen, globus pallidus and substantia nigra of rat brain, Neuropharmacology 11: 645–663.PubMedCrossRefGoogle Scholar
  16. Creese, I., and Iversen, S. D., 1975, The pharmacological and anatomical substrates of the amphetamine response in the rat, Brain Res. 83: 419–436.PubMedCrossRefGoogle Scholar
  17. Creese, I., Sibley, D. R., Hamblin, M. W., and Leff, S. E., 1983, The classification of dopamine receptors, Annu. Rev. Neurosci. 6: 43–71.PubMedCrossRefGoogle Scholar
  18. Dahlström, A., and Fuxe, K., 1964, Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons, Acta. Physiol. Scand. 232 (Suppl.): 1–55.Google Scholar
  19. Dankova, J., Bedard, P,. Langelier, P., and Poirier, L. J., 1978, Dopaminergic agents and circling behavior, Gen. Pharmacol. 9: 295–302.PubMedCrossRefGoogle Scholar
  20. Erhinger, H., and Hornykiewicz, O., 1960, Verteilung von noradrenalin und dopamin (3-hydroxytyramine) in geshirn des menschen und iht verhalten bei erkrangungen des extrapyramidalen systems, Klin. Wochenschir. 38: 1236–1239.CrossRefGoogle Scholar
  21. Fog, R., Randrup, A., and Parkkenberg, H., 1967, Aminergic mechanisms in corpus striatum and amphetamine-induced stereotyped behaviour, Psychopharmacol. 11: 179–193.CrossRefGoogle Scholar
  22. Fog, R., Randrup, A., and Parkkenberg, H., 1968, Neuroleptic action of quaternary chlorpromazine and related drugs injected into various brain areas in rats, Psychopharmacology 12: 428–432.CrossRefGoogle Scholar
  23. Gerlach, J., Bjorndal, N., and Christensson, E., 1984, Methylphenidate, apomorphine, THIP, and diazepam in monkeys: Dopamine-GABA behavior related to psychoses and tardive dyskinesia, Psychopharmacology 82: 131–134.PubMedCrossRefGoogle Scholar
  24. Glassman, R. B., and Glassman, H. N., 1980, Oral dyskinesia in brain-damaged rats withdrawn from a neuroleptic: Implication for models of tardive dyskinesia, Psychopharmacology 69: 1925.CrossRefGoogle Scholar
  25. Glick, S. D., Jerussi, T. P., and Fleisher, L. N., 1976, Turning in circles: The neuropharmacology of rotation, Life. Sci. 18: 889–896.PubMedCrossRefGoogle Scholar
  26. Goetz, C. G., Klawans, H. L., and Carvey, P., 1983, Animals models of tardive dyskinesia: Their use in the search for new treatment methods, Mod. Prob. Pharmacopsychiatry. 21: 5–20.Google Scholar
  27. Iversen, S. D., 1977, Brain dopamine systems and behavior, in: Handbook of Psychopharmacology, Vol. 1 ( L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds.), pp. 333–374, Plenum Press, New York.CrossRefGoogle Scholar
  28. Johns, R. J., and Draper, I. T., 1964, The control of movement in normal subjects, Bull. Johns Hopkins Hosp. 115: 447–464.PubMedGoogle Scholar
  29. Kelly, P. H., 1977, Drug-induced motor behavior, in: Handbook of Psychopharmacology, Vol. 8 ( L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds.), pp. 295–320, Plenum Press, New York.Google Scholar
  30. Kelly, P. H., Seviour, P. W., and Iversen, S. D., 1975, Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum, Brain Res. 94: 507–522.PubMedCrossRefGoogle Scholar
  31. Klawans, H. L., Jr., 1973, The pharmacology of tardive dyskinesias, Am. J. Psychiatry. 130: 8286.Google Scholar
  32. Knutsson, E., 1975, An analysis of Parkinsonian gait, Brain 95: 475–486.CrossRefGoogle Scholar
  33. Knutsson, E., and Martensson, A., 1971, Quantitative effects of L-dopa on different types of movements and muscle tone in Parkinsonian patients, Scand. J. Rehab. Med. 3: 121–130.Google Scholar
  34. Langrall, H. M., and Joseph, C., 1972, Evaluation of safety and efficacy of levodopa in Parkinson’s disease and syndrome, Neurology 22: 1–14.Google Scholar
  35. Leanderson, R., Meyerson, B. A., and Persson, A., 1972, Lip muscle function in parkinsonian dysarthria, Acta. Otolaryng. 74: 350–357.PubMedCrossRefGoogle Scholar
  36. Leff, S. E., and Creese, I., 1983, Dopamine receptors re-examined, Trends in Pharmacological Science 4 (11): 463–467.CrossRefGoogle Scholar
  37. Liebman, J., and Neale, R., 1980, Neuroleptic-induced acute dyskinesias in squirrel monkeys: Correlation with propensity to cause extra-pyramidal side effects, Psychopharmacology 68: 2529.CrossRefGoogle Scholar
  38. Lindvall, O., and Björklund, A., 1978, Anatomy of the dopaminergic neuron systems in the rat brain, Adv. Biochem. Psychopharmacol. 19: 1–23.PubMedGoogle Scholar
  39. Lloyd, K. G., Broekkamp, C. L. E., Cathala, F., Worms, P., Goldstein, M., and Asano, T., 1981, Animal models for the prediction and prevention of dyskinesias induced by dopaminergic drugs, in: Apomorphine and Other Dopaminomimetics: Clinical Pharmacology, Vol. 2 ( G. U. Corsini and G. L. Gessa, eds.), pp. 123–133, Raven Press, New York.Google Scholar
  40. Moore, R. Y., and Bloom, F. E., 1978, Central catecholamine neuron systems: Anatomy and physiology of the dopamine systems, Ann. Rev. Neurosci. 1: 129–169.PubMedCrossRefGoogle Scholar
  41. Naylor, R. J., and Olley, J. E., 1972, Modification of the behavioural changes induced by amphetamine in the rat lesions in the caudate nucleus, the caudate-putamen and globus pallidus, Neuropharmacology 11: 91–99.PubMedCrossRefGoogle Scholar
  42. Neale, R., Fallon, S., Gerhardt, S., and Liebman, J. M., 1981, Acute dyskinesias in monkeys elicited by halopemide, mezilamine, and the antidyskinetic drugs, oxiperomide and tiapride, Psychopharmacology 75: 254–257.PubMedCrossRefGoogle Scholar
  43. Neale, R., Gerhardt, S., and Liebman, J. M., 1984, Effects of dopamine agonists, catecholamine depletors, and cholinergic and GABAergic drugs in acute dyskinesias in squirrel monkeys, Psychopharmacology 82: 20–26.Google Scholar
  44. Peaston, M. J. T., and Bianchine, J. R., 1970, Metabolic studies and clinical observations during L-dopa treatment of Parkinson’s disease, Br. Med. J. 1: 400.PubMedCrossRefGoogle Scholar
  45. Pycock, C. J., 1980, Turning behaviour in animals, Neuroscience 5: 461–514.PubMedCrossRefGoogle Scholar
  46. Rose, F. C., and Capildeo, R. (eds.), 1981, Research Progress in Parkinson’s Disease, Pitman Books Limited, London.Google Scholar
  47. Schwab, R. S., 1964, Problems in clinical estimation of rigidity, Clin. Pharmacol. Ther. 5: 942–946.Google Scholar
  48. Seeman, P., 1980, Brain dopamine receptors, Pharmacol. Rev. 32: 229–313.PubMedGoogle Scholar
  49. Tarsy, D., and Baldessarini, R. J., 1984, Tardive dyskinesia, Annu. Rev. Med. 35: 605–623.PubMedCrossRefGoogle Scholar
  50. Ungerstedt, U., 1971, Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour, Acta. Physiol. Scand 367 (Suppl.): 49–68.Google Scholar
  51. Velasco, F., and Velasco, M., 1973, A quantitative evaluation of the effects of L-DOPA on Parkinson’s disease, Neuropharmacology 12: 89–99.PubMedCrossRefGoogle Scholar
  52. Waddington, J. L., Cross, A. J., Gamble, S. J., and Bourne, R. C., 1982, Spontaneous orofacial dyskinesia and dopaminergic function in rats after six months of neuroleptic treatment, Science 220: 530–532.CrossRefGoogle Scholar
  53. Weiss, B., Santelli, S., and Lusink, G., 1977, Movement disorders induced in monkeys by chronic haloperidol treatment, Psychopharmacology 53: 289–293.PubMedCrossRefGoogle Scholar
  54. Weissman, A., Koe, B. K., and Tenen, S. S., 1966, Anti-amphetamine effects following inhibition of tyrosine hydroxylase, J. Pharmacol. Exp. Ther. 151: 339–352.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • J. R. Bianchine
    • 1
  • R. D. Schwartz
    • 1
  • C. W. RichardIII
    • 1
  1. 1.Department of Pharmacology, College of MedicineThe Ohio State UniversityColumbusUSA

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