Tags

Type your tag names separated by a space and hit enter

Molecular basis of levodopa-induced dyskinesias.
Ann Neurol. 2000 Apr; 47(4 Suppl 1):S70-8.AN

Abstract

A series of experiments were performed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism for the purpose of understanding the mechanism of dopaminergic dyskinesias. Dyskinesias can be induced in this model by de novo treatment with levodopa, or selective D1 or D2 agonists, provided the drugs are short acting and administered in the pulsatile mode. Biochemical analysis of the brains revealed several alterations in dopamine receptor-binding and messenger RNA message following denervation and dopaminergic treatment, but none that clearly correlated with the presence of dyskinesias. On the other hand, gamma-aminobutyric acid (GABA)A binding was increased in the internal segment of the globus pallidus of dyskinetic MPTP monkeys. This was observed consistently and could be associated with an exaggerated response to GABAergic inhibitory inputs in this strategic structure. Increased preproenkephalin message was also found to correlate with dyskinesias and may be linked to changes in GABA receptors. Treatments that caused dyskinesias induced, in the striatum, chronic Fos proteins of the deltaFosB family which, when coupled with Jun-D, form AP-1 complexes that can affect several genes, including enkephalin and N-methyl-D-aspartate receptor. We suggest that levodopa-induced dyskinesias represent a form of pathological learning, which results from deficient gating of glutamatergic inputs to the striatum by dopamine.

Authors+Show Affiliations

Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, and Faculty of Pharmacy, Laval University, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10762134

Citation

Calon, F, et al. "Molecular Basis of Levodopa-induced Dyskinesias." Annals of Neurology, vol. 47, no. 4 Suppl 1, 2000, pp. S70-8.
Calon F, Grondin R, Morissette M, et al. Molecular basis of levodopa-induced dyskinesias. Ann Neurol. 2000;47(4 Suppl 1):S70-8.
Calon, F., Grondin, R., Morissette, M., Goulet, M., Blanchet, P. J., Di Paolo, T., & Bédard, P. J. (2000). Molecular basis of levodopa-induced dyskinesias. Annals of Neurology, 47(4 Suppl 1), S70-8.
Calon F, et al. Molecular Basis of Levodopa-induced Dyskinesias. Ann Neurol. 2000;47(4 Suppl 1):S70-8. PubMed PMID: 10762134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular basis of levodopa-induced dyskinesias. AU - Calon,F, AU - Grondin,R, AU - Morissette,M, AU - Goulet,M, AU - Blanchet,P J, AU - Di Paolo,T, AU - Bédard,P J, PY - 2000/4/13/pubmed PY - 2000/4/29/medline PY - 2000/4/13/entrez SP - S70 EP - 8 JF - Annals of neurology JO - Ann Neurol VL - 47 IS - 4 Suppl 1 N2 - A series of experiments were performed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism for the purpose of understanding the mechanism of dopaminergic dyskinesias. Dyskinesias can be induced in this model by de novo treatment with levodopa, or selective D1 or D2 agonists, provided the drugs are short acting and administered in the pulsatile mode. Biochemical analysis of the brains revealed several alterations in dopamine receptor-binding and messenger RNA message following denervation and dopaminergic treatment, but none that clearly correlated with the presence of dyskinesias. On the other hand, gamma-aminobutyric acid (GABA)A binding was increased in the internal segment of the globus pallidus of dyskinetic MPTP monkeys. This was observed consistently and could be associated with an exaggerated response to GABAergic inhibitory inputs in this strategic structure. Increased preproenkephalin message was also found to correlate with dyskinesias and may be linked to changes in GABA receptors. Treatments that caused dyskinesias induced, in the striatum, chronic Fos proteins of the deltaFosB family which, when coupled with Jun-D, form AP-1 complexes that can affect several genes, including enkephalin and N-methyl-D-aspartate receptor. We suggest that levodopa-induced dyskinesias represent a form of pathological learning, which results from deficient gating of glutamatergic inputs to the striatum by dopamine. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/10762134/Molecular_basis_of_levodopa_induced_dyskinesias_ DB - PRIME DP - Unbound Medicine ER -