Hostname: page-component-848d4c4894-xm8r8 Total loading time: 0 Render date: 2024-06-16T15:10:30.808Z Has data issue: false hasContentIssue false
  • English
  • Français

Levodopa-Induced Dyskinesia: Facts and Fancy. What Does the MPTP Monkey Model Tell Us?

Published online by Cambridge University Press:  18 September 2015

Paul J. Bédard ,
Baltazar Gomez Mancilla ,
Pierre Blanchette ,
Céline Gagnon  and
Thérèse Di Paolo
Paul J. Bédard*
Affiliation:
Centre de recherche en neurobiologie (P.J.B., B.G.M., P.B.) et Département des Sciences neurologiques (P.J.B., P.B.), Hôpital de l’Enfant-Jésus Centre de recherche en endocrinologie moléculaire, Centre Hospitalier de l’Université Laval (C.G., T.D.P.); Département de Pharmacologie, Faculté de Médecine (P.J.B., B.G.M., P.B.) et École de Pharmacie (C.G., T.D.P), Université Laval
Baltazar Gomez Mancilla
Affiliation:
Centre de recherche en neurobiologie (P.J.B., B.G.M., P.B.) et Département des Sciences neurologiques (P.J.B., P.B.), Hôpital de l’Enfant-Jésus Centre de recherche en endocrinologie moléculaire, Centre Hospitalier de l’Université Laval (C.G., T.D.P.); Département de Pharmacologie, Faculté de Médecine (P.J.B., B.G.M., P.B.) et École de Pharmacie (C.G., T.D.P), Université Laval
Pierre Blanchette
Affiliation:
Centre de recherche en neurobiologie (P.J.B., B.G.M., P.B.) et Département des Sciences neurologiques (P.J.B., P.B.), Hôpital de l’Enfant-Jésus Centre de recherche en endocrinologie moléculaire, Centre Hospitalier de l’Université Laval (C.G., T.D.P.); Département de Pharmacologie, Faculté de Médecine (P.J.B., B.G.M., P.B.) et École de Pharmacie (C.G., T.D.P), Université Laval
Céline Gagnon
Affiliation:
Centre de recherche en neurobiologie (P.J.B., B.G.M., P.B.) et Département des Sciences neurologiques (P.J.B., P.B.), Hôpital de l’Enfant-Jésus Centre de recherche en endocrinologie moléculaire, Centre Hospitalier de l’Université Laval (C.G., T.D.P.); Département de Pharmacologie, Faculté de Médecine (P.J.B., B.G.M., P.B.) et École de Pharmacie (C.G., T.D.P), Université Laval
Thérèse Di Paolo
Affiliation:
Centre de recherche en neurobiologie (P.J.B., B.G.M., P.B.) et Département des Sciences neurologiques (P.J.B., P.B.), Hôpital de l’Enfant-Jésus Centre de recherche en endocrinologie moléculaire, Centre Hospitalier de l’Université Laval (C.G., T.D.P.); Département de Pharmacologie, Faculté de Médecine (P.J.B., B.G.M., P.B.) et École de Pharmacie (C.G., T.D.P), Université Laval
*
Centre de recherche en neurobiologie, Hôpital de l’Enfant-Jésus, 1401, 18e Rue, Québec, Québec, Canada G1J IZ4
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Levodopa-induced dyskinesia, one of the most frequent long-term side effects of antiparkinsonian therapy, is often attributed to denervation supersensitivity of dopamine receptors and perhaps more specifically the D-1 receptor. The available evidence based not only on clinico-pathological studies in patients but also on results of experiments performed on methyl-phenyl-tetrahydropyridine (MPTP)-treated monkeys suggests that the mechanisms may be more complex than heretofore believed. Thus it appears that no single receptor is the sole culprit, that some form of denervation supersensitivity is probably involved but not in the form of increased density of dopamine receptors. Moreover, other neurotransmitter systems must be considered such as GABA, excitatory aminoacids and peptides. The MPTP monkey model remains very useful for predicting the potential of new drugs for inducing dyskinesia. Such trials however must be performed in drug-naive animals.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue S1: 3rd Canadian Conference on Neurodegenerative Diseases , February 1992 , pp. 134 - 137
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

1.Barbeau, A.L-dopa therapy in Parkinson’s disease: a critical review of nine years’ experience. Can Med Assoc J 1969; 101: 791–800.Google ScholarPubMed
2.Cotzias, GC, Van Woert, MH, Schiffer, LM.Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967; 276: 374–379.CrossRefGoogle ScholarPubMed
3.Langston, WJ, Ballard, P.Parkinsonism induced by l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can J Neurol Sci 1984; II: 160–165.CrossRefGoogle Scholar
4.Lees, AJ, Stern, GM.Sustained bromocriptine therapy in previously untreated patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1981; 44: 1020–1023.CrossRefGoogle ScholarPubMed
5.Rascol, A, Guiraud, B, Montrastruc, JL, et al. Long-term treatment of Parkinson’s disease with bromocriptine. J Neurol Neurosurg Psychiatry 1979; 42: 143.CrossRefGoogle ScholarPubMed
6.Rinne, UK, Combined bromocriptine-levodopa therapy early in Parkinson’s disease. Neurology 1985; 35: 1196–1198.CrossRefGoogle ScholarPubMed
7.Rinne, UK.Early combination of bromocriptine and levodopa in the treatment of Parkinson’s disease: a 5 year follow-up. Neurology 1987; 37: 826.CrossRefGoogle ScholarPubMed
8.Nutt, JG.Levodopa-induced dyskinesia. Neurology 1990; 40: 340–345.CrossRefGoogle ScholarPubMed
9.Burns, RS, Chiueh, CC, Markey, SP, et al. A primate model of parkinsonism: selective destruction of dopaminergic neurones in the pars compacta of the substantia nigra by l-methyI-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proc Natl Acad Sci U.S.A. 1983; 80: 4546–4550.CrossRefGoogle ScholarPubMed
10.Langston, J, Forno, LS, Robert, CS, et al. Selective nigral toxicity after systemic administration of MPTP in the squirrel monkey. Brain Res 1984; 292: 390–394.CrossRefGoogle ScholarPubMed
11.Bédard, PJ, Di Paolo, T, Falardeau, P, et al. Chronic treatment with L-dopa, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys: correlation with [3H] spiperone binding. Brain Res 1986; 379: 294–299.CrossRefGoogle Scholar
12.Clarke, CE, Boyce, S, Robertson, RG, et al. Drug-induced dyskinesia in primates rendered hemiparkinsonian by intracarotid administration of l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). J Neurol Sci 1989; 90: 307–314.CrossRefGoogle Scholar
13.Jenner, P, Rupniak, NMJ, Rose, S, et al. l-Methyl-4-pheny I-1, 2, 3, 6-tetrahydropyridine-induced parkinsonism in the common marmoset. Neurosci Lett 1984; 51: 47–53.Google Scholar
14.Schneider, JS.Levodopa-induced dyskinesia in parkinsonian monkeys: relationship to extent of nigrostriatal damage. Pharmacol Biochem Behav 1989; 34: 193–196.CrossRefGoogle ScholarPubMed
15.Lavoie, B, Parent, A, Bédard, PJ.Effect of dopamine denervation on striatal peptide expression in parkinsonian monkeys. Can J Neurol Sci (in press).Google Scholar
16.Tremblay, L, Filion, M, Responses of pallidal neurons to striatal stimulation in intact waking monkeys. Brain Res 1989; 498: 1–16.CrossRefGoogle ScholarPubMed
17.Di Paolo, T, Bédard, PJ, Daigle, M, et al. Long-term effects of MPTP on central and peripheral catecholamine and indoleamine concentrations in monkeys. Brain Res 1986; 379: 286.CrossRefGoogle ScholarPubMed
18.Falardeau, P, Bouchard, S, Bédard, PJ, et al. Behavioural and bio-chemical effect of chronic treatment with D1 and/or D2 dopamine agonists in MPTP monkeys. Eur J Pharmacol 1988; 150: 59–66.CrossRefGoogle ScholarPubMed
19.Falardeau, P, Bédard, PJ, Di Paolo, T.Relation between brain dopamine loss and D2 dopamine receptor density in MPTP monkeys. Neurosci Lett 1988; 86: 225–229.CrossRefGoogle ScholarPubMed
20.Rouillard, C, Bédard, PJ, Di Paolo, T.Behavioral and biochemical effect of chronic treatment of MPTP-monkeys with bromocriptine alone or in combination with SKF-38393. Eur J Pharmacol 1990; 185: 209–215.CrossRefGoogle ScholarPubMed
21.Lee, T, Seeman, P, Rajput, A, et al. Receptor basis for dopaminergic supersensitivity in Parkinson’s disease. Nature (Lond) 1978; 273: 59–61.CrossRefGoogle ScholarPubMed
22.Bokobza, B, Ruberg, M, Scatton, B, et al. (3H)Spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 1984; 99: 167–175.CrossRefGoogle Scholar
23.Guttman, M, Seeman, P.L-Dopa reverses the elevated density of D2 dopamine receptors in Parkinson’s diseased striatum. J Neural Transm 1985; 64: 93–104.CrossRefGoogle ScholarPubMed
24.Raisman, R, Cash, R, Ruberg, M, et al. Binding of (3H)-SCH23390 to D1 receptors in the putamen of control and parkinsonian subjects. Eur J Pharmacol 1985; 113: 467–468.CrossRefGoogle Scholar
25.Rinne, JO, Rinne, JK, Laakso, K, et al. Dopamine DI receptors in the parkinsonian brain. Brain Res 1985; 359: 306–310.CrossRefGoogle Scholar
26.Seeman, P, Bzowej, NH, Guan, HC, et al. Human brain D1 and D2 dopamine receptors in Schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s diseases. Neuropsycopharmacology 1987; 1: 5–15.CrossRefGoogle ScholarPubMed
27.Boyce, S, Rupniak, NMJ, Steventon, MJ, et al. Nigrostriatal damage is required for induction of dyskinesias by L-Dopa in squirrel monkeys. Clin Neuropharmacol 1990; 13: 448–458.CrossRefGoogle ScholarPubMed
28.Gagnon, C, Bédard, PJ, Di Paolo, T.Effect of chronic treatment of MPTP monkeys with dopamine D-1 and/or D-2 receptor agonists. Eur J Pharmacol 1990; 178: 115–120.CrossRefGoogle ScholarPubMed
29.Robertson, GS, Robertson, HA.D1 and D2 dopamine agonist synergism: separate sites of action. Trends Pharmacol Sci 1987; 8: 295–299.CrossRefGoogle Scholar
30.Parent, A, Smith, Y.Differential dopaminergic innervation of the two pallidal segments in the squirrel monkey (Saimiri Sciureus). Brain Res 1986; 426: 397–400.CrossRefGoogle Scholar
31.Parent, A, Lavoie, B, Smith, Y, et al. The dopaminergic nigropallidal projection in primates: distinct cellular origin and relative sparing in MPTP-treated monkeys. In: Streifler, MB, Korczyn, A, Melamed, E., Youdim, MBH, eds. Advances in Neurology. New York: Raven Press, 1990; 53: 111–116.Google Scholar
32.Robertson, RG, Clarke, CA, Boyce, S, et al. The role of striopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H] flunitrazepam autoradiography. Brain Res 1990; 531: 95–104.CrossRefGoogle Scholar
33.Boyce, S, Rupniak, NMJ, Steventon, MJ, et al. Differential effects of D1 and D2 agonists in MPTP-treated primates. Neurology 1990; 40: 927–934.CrossRefGoogle ScholarPubMed
34.Close, SP, Marriott, AS, Pay, S.Failure of SKF-38393-A to relieve parkinsonian symptoms induced by MPTP in the marmoset. Br J Pharmacol 1985; 85: 320–322.CrossRefGoogle ScholarPubMed
35.Nomoto, M, Jenner, P, Marsden, CD.The dopamine D-2 agonist LY-131865 but not the D-1 agonist SKF-38393 reverses parkinsonism induced by l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridinc (MPTP) in the common marmoset. Neurosci Lett 1985; 57: 37–41.CrossRefGoogle Scholar
36.Markstein, R, Seilers, MP, Vigault, JM, et al. Pharmacological properties of CY-208243 a novel D1 agonist. In: Sandler, M, Dahlstrom, A, Belkmaker, RH, eds. Progress in catecholamine research Part B. New York: Alan R. Liss, 1988.Google Scholar
37.Jackson, DM, Jenkins, OF, Ross, SB.The motor effects of bromocriptine: a review. Psychopharmacology 1988; 95: 433–446.CrossRefGoogle ScholarPubMed