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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1630062
- author
- Kobylecki, Christopher
; Cenci Nilsson, Angela
LU
; Crossman, Alan R.
and Ravenscroft, Paula
- organization
- publishing date
- 2010
- 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
- pmid:20456008
- 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
- 2016-04-01 14:10:30
- date last changed
- 2022-04-06 17:11:39
@article{b03f13f1-eab7-45e5-8455-077fcac645a5,
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 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.}},
author = {{Kobylecki, Christopher and Cenci Nilsson, Angela and Crossman, Alan R. and Ravenscroft, Paula}},
issn = {{1471-4159}},
keywords = {{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}},
doi = {{10.1111/j.1471-4159.2010.06776.x}},
volume = {{114}},
year = {{2010}},
}