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Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease.
J Neurochem. 2010 Jul; 114(2):499-511.JN

Abstract

Overactivity of striatal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors is implicated in the pathophysiology of L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we evaluated the behavioural and molecular effects of acute and chronic blockade of Ca(2+)-permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca(2+)-permeable AMPA receptor antagonist 1-trimethylammonio-5-(1-adamantane-methylammoniopentane) dibromide hydrobromide (IEM 1460) on abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat and LID in the MPTP-lesioned non-human primate were assessed. Subsequently, the effects of chronic treatment of 6-OHDA-lesioned rats with vehicle, L-DOPA/benserazide (6/15 mg/kg, i.p.) + vehicle or L-DOPA + IEM 1460 (3 mg/kg, i.p.) on behavioural and molecular correlates of priming for LID were evaluated. In the 6-OHDA-lesioned rat and MPTP-lesioned non-human primate, acute treatment with IEM 1460 (1-3 mg/kg) dose-dependently reduced LID without adverse effects on motor performance. Chronic co-treatment for 21 days with IEM 1460 reduced the induction of AIMs by L-DOPA in the 6-OHDA-lesioned rat without affecting peak rotarod performance, and attenuated AIMs score by 75% following l-DOPA challenge (p < 0.05). Chronic IEM 1460 treatment reversed L-DOPA-induced up-regulation of pre-proenkephalin-A, and normalised pre-proenkephalin-B mRNA expression in the lateral striatum, indicating an inhibition of both behavioural and molecular correlates of priming. These data suggest that Ca(2+)-permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti-dyskinetic therapies.

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Authors+Show Affiliations

Kobylecki C
Faculty of Life Sciences, University of Manchester, Manchester, UK. christopher.kobylecki@manchester.ac.uk
Cenci MA
No affiliation info available
Crossman AR
No affiliation info available
Ravenscroft P
No affiliation info available

MeSH

AdamantaneAnimalsAntiparkinson AgentsBehavior, AnimalBenserazideBrainCalciumCallithrixDyskinesia, Drug-InducedEnkephalinsLevodopaMaleMotor ActivityOxidopamineParkinson DiseaseProtein PrecursorsRatsRats, Sprague-DawleyReceptors, AMPA

Pub Type(s)

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

Language

eng

PubMed ID

20456008

Citation

Kobylecki, Christopher, et al. "Calcium-permeable AMPA Receptors Are Involved in the Induction and Expression of l-DOPA-induced Dyskinesia in Parkinson's Disease." Journal of Neurochemistry, vol. 114, no. 2, 2010, pp. 499-511.
Kobylecki C, Cenci MA, Crossman AR, et al. Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease. J Neurochem. 2010;114(2):499-511.
Kobylecki, C., Cenci, M. A., Crossman, A. R., & Ravenscroft, P. (2010). Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease. Journal of Neurochemistry, 114(2), 499-511. https://doi.org/10.1111/j.1471-4159.2010.06776.x
Kobylecki C, et al. Calcium-permeable AMPA Receptors Are Involved in the Induction and Expression of l-DOPA-induced Dyskinesia in Parkinson's Disease. J Neurochem. 2010;114(2):499-511. PubMed PMID: 20456008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease. AU - Kobylecki,Christopher, AU - Cenci,M Angela, AU - Crossman,Alan R, AU - Ravenscroft,Paula, Y1 - 2010/04/28/ PY - 2010/5/12/entrez PY - 2010/5/12/pubmed PY - 2010/8/24/medline SP - 499 EP - 511 JF - Journal of neurochemistry JO - J Neurochem VL - 114 IS - 2 N2 - Overactivity of striatal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors is implicated in the pathophysiology of L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we evaluated the behavioural and molecular effects of acute and chronic blockade of Ca(2+)-permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca(2+)-permeable AMPA receptor antagonist 1-trimethylammonio-5-(1-adamantane-methylammoniopentane) dibromide hydrobromide (IEM 1460) on abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat and LID in the MPTP-lesioned non-human primate were assessed. Subsequently, the effects of chronic treatment of 6-OHDA-lesioned rats with vehicle, L-DOPA/benserazide (6/15 mg/kg, i.p.) + vehicle or L-DOPA + IEM 1460 (3 mg/kg, i.p.) on behavioural and molecular correlates of priming for LID were evaluated. In the 6-OHDA-lesioned rat and MPTP-lesioned non-human primate, acute treatment with IEM 1460 (1-3 mg/kg) dose-dependently reduced LID without adverse effects on motor performance. Chronic co-treatment for 21 days with IEM 1460 reduced the induction of AIMs by L-DOPA in the 6-OHDA-lesioned rat without affecting peak rotarod performance, and attenuated AIMs score by 75% following l-DOPA challenge (p < 0.05). Chronic IEM 1460 treatment reversed L-DOPA-induced up-regulation of pre-proenkephalin-A, and normalised pre-proenkephalin-B mRNA expression in the lateral striatum, indicating an inhibition of both behavioural and molecular correlates of priming. These data suggest that Ca(2+)-permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti-dyskinetic therapies. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/20456008/Calcium_permeable_AMPA_receptors_are_involved_in_the_induction_and_expression_of_l_DOPA_induced_dyskinesia_in_Parkinson's_disease_ L2 - https://doi.org/10.1111/j.1471-4159.2010.06776.x DB - PRIME DP - Unbound Medicine ER -