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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

Molecular Endocrinology and Oncology Research Centre, Laval University Medical Centre, Quebec, 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

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_ L2 - https://doi.org/10.1002/mds.20654 DB - PRIME DP - Unbound Medicine ER -