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Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease

Kobylecki, Christopher; Cenci Nilsson, Angela LU ; Crossman, Alan R. and Ravenscroft, Paula (2010) In Journal of Neurochemistry 114(2). p.499-511
Abstract
P>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 Ca2+-permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca2+-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... (More)
P>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 Ca2+-permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca2+-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 Ca2+-permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti-dyskinetic therapies. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Parkinson's disease, l-DOPA-induced dyskinesia, glutamate, calcium, animal models, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
in
Journal of Neurochemistry
volume
114
issue
2
pages
499 - 511
publisher
Wiley-Blackwell
external identifiers
  • wos:000279077900015
  • scopus:77953843122
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2010.06776.x
language
English
LU publication?
yes
id
b03f13f1-eab7-45e5-8455-077fcac645a5 (old id 1630062)
date added to LUP
2010-07-22 09:59:03
date last changed
2018-05-29 10:46:04
@article{b03f13f1-eab7-45e5-8455-077fcac645a5,
  abstract     = {P&gt;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 Ca2+-permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca2+-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 &lt; 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 Ca2+-permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti-dyskinetic therapies.},
  author       = {Kobylecki, Christopher and Cenci Nilsson, Angela and Crossman, Alan R. and Ravenscroft, Paula},
  issn         = {1471-4159},
  keyword      = {Parkinson's disease,l-DOPA-induced dyskinesia,glutamate,calcium,animal models,alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid},
  language     = {eng},
  number       = {2},
  pages        = {499--511},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2010.06776.x},
  volume       = {114},
  year         = {2010},
}