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Investigating levodopa-induced dyskinesias in the parkinsonian primate.
Ann Neurol. 2000 Apr; 47(4 Suppl 1):S79-89.AN

Abstract

Research into the cause of dyskinesias arising from levodopa treatment has been vexingly limited, partly due to the lack of an inexpensive and widely available animal model. Rodents do not develop levodopa-induced dyskinesias in a clinically recognizable form. However, nonhuman primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism readily develop levodopa-induced dyskinesias that are virtually indistinguishable from those seen in patients with Parkinson's disease. We have developed and validated a five-point Global Primate Dyskinesia Rating Scale to accurately measure these dyskinesias. Monkeys with MPTP-induced parkinsonism were then investigated to evaluate the relationship between dyskinesias, parkinsonism and severity of the nigrostriatal lesion. All parkinsonian animals were responsive to levodopa, and developed dyskinesias within 2-3 days of levodopa administration. Monkeys treated with only a single injection of MPTP also developed dyskinesias, even though they were not parkinsonian. It would appear that there is a different threshold of striatal dopamine depletion for parkinsonism and dyskinesias in the monkey. Finally, three hypotheses, put forward to explain the genesis of dyskinesias, are reviewed, and various experimental approaches suggested for each.

Authors+Show Affiliations

The Parkinson's Institute, Sunnyvale, CA 94089-1605, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

10762135

Citation

Langston, J W., et al. "Investigating Levodopa-induced Dyskinesias in the Parkinsonian Primate." Annals of Neurology, vol. 47, no. 4 Suppl 1, 2000, pp. S79-89.
Langston JW, Quik M, Petzinger G, et al. Investigating levodopa-induced dyskinesias in the parkinsonian primate. Ann Neurol. 2000;47(4 Suppl 1):S79-89.
Langston, J. W., Quik, M., Petzinger, G., Jakowec, M., & Di Monte, D. A. (2000). Investigating levodopa-induced dyskinesias in the parkinsonian primate. Annals of Neurology, 47(4 Suppl 1), S79-89.
Langston JW, et al. Investigating Levodopa-induced Dyskinesias in the Parkinsonian Primate. Ann Neurol. 2000;47(4 Suppl 1):S79-89. PubMed PMID: 10762135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigating levodopa-induced dyskinesias in the parkinsonian primate. AU - Langston,J W, AU - Quik,M, AU - Petzinger,G, AU - Jakowec,M, AU - Di Monte,D A, PY - 2000/4/13/pubmed PY - 2000/4/29/medline PY - 2000/4/13/entrez SP - S79 EP - 89 JF - Annals of neurology JO - Ann Neurol VL - 47 IS - 4 Suppl 1 N2 - Research into the cause of dyskinesias arising from levodopa treatment has been vexingly limited, partly due to the lack of an inexpensive and widely available animal model. Rodents do not develop levodopa-induced dyskinesias in a clinically recognizable form. However, nonhuman primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism readily develop levodopa-induced dyskinesias that are virtually indistinguishable from those seen in patients with Parkinson's disease. We have developed and validated a five-point Global Primate Dyskinesia Rating Scale to accurately measure these dyskinesias. Monkeys with MPTP-induced parkinsonism were then investigated to evaluate the relationship between dyskinesias, parkinsonism and severity of the nigrostriatal lesion. All parkinsonian animals were responsive to levodopa, and developed dyskinesias within 2-3 days of levodopa administration. Monkeys treated with only a single injection of MPTP also developed dyskinesias, even though they were not parkinsonian. It would appear that there is a different threshold of striatal dopamine depletion for parkinsonism and dyskinesias in the monkey. Finally, three hypotheses, put forward to explain the genesis of dyskinesias, are reviewed, and various experimental approaches suggested for each. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/10762135/Investigating_levodopa_induced_dyskinesias_in_the_parkinsonian_primate_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=2000&volume=47&issue=4 Suppl 1&spage=S79 DB - PRIME DP - Unbound Medicine ER -