Journal of Molecular Neuroscience

, Volume 38, Issue 2, pp 128–142 | Cite as

Implication of NMDA Receptors in the Antidyskinetic Activity of Cabergoline, CI-1041, and Ro 61-8048 in MPTP Monkeys with Levodopa-induced Dyskinesias

  • Bazoumana Ouattara
  • Samah Belkhir
  • Marc Morissette
  • Mehdi Dridi
  • Pershia Samadi
  • Laurent Grégoire
  • Leonard T. Meltzer
  • Thérèse Di Paolo
Article

Abstract

This study assessed striatal N-methyl-D-aspartate (NMDA) glutamate receptors of 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys with levodopa (L-DOPA)-induced dyskinesias (LID). In a first experiment, four MPTP monkeys receiving L-DOPA/Benserazide alone developed dyskinesias. Four MPTP monkeys received L-DOPA/Benserazide plus CI-1041 an NMDA antagonist selective for NR1/NR2B and four were treated with L-DOPA/Benserazide plus a small dose of cabergoline; one monkey of each group developed mild dyskinesias at the end of treatment. In a second experiment, a kynurenine 3-hydroxylase inhibitor Ro 61-8048, combined with L-DOPA/Benserazide, reduced dyskinesias in MPTP monkeys. Drug-treated MPTP monkeys were compared to intact monkeys and saline-treated MPTP monkeys. Glutamate receptors were investigated by autoradiography using [3H]CGP-39653 (NR1/NR2A antagonist) and [3H]Ro25-6981 (NR1/NR2B antagonist). In general, striatal [3H]CGP-39653 specific binding was unaltered in all experimental groups. MPTP lesion decreased striatal [3H]Ro25-6981 specific binding; these levels were enhanced in the L-DOPA-alone-treated MPTP monkeys and decreased in antidyskinetic drugs treated monkeys. Maximal dyskinesias scores of the MPTP monkeys correlated significantly with [3H]Ro25-6981 specific binding in the rostral and caudal striatum. Hence, MPTP lesion, L-DOPA treatment and prevention of LID with CI-1041 and cabergoline, or reduction with Ro 61-8048 were associated with modulation of NR2B/NMDA glutamate receptors.

Keywords

NMDA receptor L-DOPA Dyskinesia MPTP Monkeys Cabergoline CI-1041 Ro 61-8048 

Abbreviations

DA

Dopamine

DAT

Dopamine Transporter

DOPAC

3, 4 dihydroxyphenylacetic acid

HVA

Homovanillic acid

L-DOPA

Levodopa

LID

L-DOPA-induced dyskinesias

LTD

long term depression

LTP

long term potentiation

3-MT

3-methoxytyramine

NMDA

N-methyl-D-aspartate

PD

Parkinson’s disease

Notes

Acknowledgements

This research was funded by a grant from the Canadian Institutes of Health Research to TDP. BO was supported by the Government of Ivory Coast and SB by the Government of Tunisia.

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Copyright information

© Humana Press 2008

Authors and Affiliations

  • Bazoumana Ouattara
    • 1
    • 2
  • Samah Belkhir
    • 1
    • 2
  • Marc Morissette
    • 1
    • 2
  • Mehdi Dridi
    • 1
    • 2
  • Pershia Samadi
    • 1
    • 2
  • Laurent Grégoire
    • 1
    • 2
  • Leonard T. Meltzer
    • 3
  • Thérèse Di Paolo
    • 1
    • 2
  1. 1.Molecular Endocrinology and Oncology Research CenterLaval University Medical Center, CHULQuebecCanada
  2. 2.Faculty of PharmacyLaval UniversityQuebecCanada
  3. 3.Global Research & DevelopmentPfizerAnn ArborUSA

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