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Prevention of levodopa-induced dyskinesias by a selective NR1A/2B N-methyl-D-aspartate receptor antagonist in parkinsonian monkeys: implication of preproenkephalin.
Mov Disord. 2006 Jan; 21(1):9-17.MD

Abstract

Enkephalin is reported to play an important role in the pathophysiology of levodopa (LD) -induced dyskinesias. The present study investigated the effect of chronic treatment with a selective NR1A/2B N-methyl-D-aspartate (NMDA) receptor antagonist, CI-1041, on the expression of preproenkephalin-A (PPE-A) in brains of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treated monkeys in relation to the development of LD-induced dyskinesias. Four MPTP-monkeys received LD/benserazide alone; they all developed dyskinesias. Four other MPTP-monkeys received LD/benserazide plus CI-1041; only one of them developed mild dyskinesias at the end of the fourth week of treatment. Four normal monkeys and four saline-treated MPTP monkeys were also included. MPTP-treated monkeys had extensive and similar striatal dopamine denervation. An increase of PPE-A mRNA levels assayed by in situ hybridization was observed in the lateral putamen (rostral and caudal) and caudate nucleus (rostral) of saline-treated MPTP monkeys compared to controls, whereas no change or a small increase was observed in their medial parts. Striatal PPE-A mRNA levels remained elevated in LD-treated MPTP monkeys, whereas cotreatment with CI-1041 brought them back to control values. These findings suggest that chronic blockade of striatal NR1A/2B NMDA receptors with CI-1041 normalizes PPE-A mRNA expression and prevents the development of LD-induced dyskinesias in an animal model of Parkinson disease.

Authors+Show Affiliations

Morissette M
Molecular Endocrinology and Oncology Research Centre, Laval University Medical Centre, Quebec, Canada.
Dridi M
No affiliation info available
Calon F
No affiliation info available
Hadj Tahar A
No affiliation info available
Meltzer LT
No affiliation info available
Bédard PJ
No affiliation info available
Di Paolo T
No affiliation info available

MeSH

AnimalsAntiparkinson AgentsBenserazideBenzoxazolesCorpus StriatumDopamineDrug Therapy, CombinationDyskinesia, Drug-InducedEnkephalinsFemaleGene ExpressionLevodopaMacaca fascicularisParkinsonian DisordersPiperidinesProtein PrecursorsRNA, MessengerReceptors, N-Methyl-D-Aspartate

Pub Type(s)

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

Language

eng

PubMed ID

16127720

Citation

Morissette, Marc, et al. "Prevention of Levodopa-induced Dyskinesias By a Selective NR1A/2B N-methyl-D-aspartate Receptor Antagonist in Parkinsonian Monkeys: Implication of Preproenkephalin." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 21, no. 1, 2006, pp. 9-17.
Morissette M, Dridi M, Calon F, et al. Prevention of levodopa-induced dyskinesias by a selective NR1A/2B N-methyl-D-aspartate receptor antagonist in parkinsonian monkeys: implication of preproenkephalin. Mov Disord. 2006;21(1):9-17.
Morissette, M., Dridi, M., Calon, F., Hadj Tahar, A., Meltzer, L. T., Bédard, P. J., & Di Paolo, T. (2006). Prevention of levodopa-induced dyskinesias by a selective NR1A/2B N-methyl-D-aspartate receptor antagonist in parkinsonian monkeys: implication of preproenkephalin. Movement Disorders : Official Journal of the Movement Disorder Society, 21(1), 9-17.
Morissette M, et al. Prevention of Levodopa-induced Dyskinesias By a Selective NR1A/2B N-methyl-D-aspartate Receptor Antagonist in Parkinsonian Monkeys: Implication of Preproenkephalin. Mov Disord. 2006;21(1):9-17. PubMed PMID: 16127720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevention of levodopa-induced dyskinesias by a selective NR1A/2B N-methyl-D-aspartate receptor antagonist in parkinsonian monkeys: implication of preproenkephalin. AU - Morissette,Marc, AU - Dridi,Mehdi, AU - Calon,Frédéric, AU - Hadj Tahar,Abdallah, AU - Meltzer,Leonard T, AU - Bédard,Paul J, AU - Di Paolo,Thérèse, PY - 2005/8/30/pubmed PY - 2006/7/4/medline PY - 2005/8/30/entrez SP - 9 EP - 17 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 21 IS - 1 N2 - Enkephalin is reported to play an important role in the pathophysiology of levodopa (LD) -induced dyskinesias. The present study investigated the effect of chronic treatment with a selective NR1A/2B N-methyl-D-aspartate (NMDA) receptor antagonist, CI-1041, on the expression of preproenkephalin-A (PPE-A) in brains of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treated monkeys in relation to the development of LD-induced dyskinesias. Four MPTP-monkeys received LD/benserazide alone; they all developed dyskinesias. Four other MPTP-monkeys received LD/benserazide plus CI-1041; only one of them developed mild dyskinesias at the end of the fourth week of treatment. Four normal monkeys and four saline-treated MPTP monkeys were also included. MPTP-treated monkeys had extensive and similar striatal dopamine denervation. An increase of PPE-A mRNA levels assayed by in situ hybridization was observed in the lateral putamen (rostral and caudal) and caudate nucleus (rostral) of saline-treated MPTP monkeys compared to controls, whereas no change or a small increase was observed in their medial parts. Striatal PPE-A mRNA levels remained elevated in LD-treated MPTP monkeys, whereas cotreatment with CI-1041 brought them back to control values. These findings suggest that chronic blockade of striatal NR1A/2B NMDA receptors with CI-1041 normalizes PPE-A mRNA expression and prevents the development of LD-induced dyskinesias in an animal model of Parkinson disease. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/16127720/Prevention_of_levodopa_induced_dyskinesias_by_a_selective_NR1A/2B_N_methyl_D_aspartate_receptor_antagonist_in_parkinsonian_monkeys:_implication_of_preproenkephalin_ DB - PRIME DP - Unbound Medicine ER -