Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease
Dekundy, A ; Pietraszek, M ; Schaefer, D ; Cenci Nilsson, Angela LU
and Danysz, W
(2006)
In Brain Research Bulletin
69(3).
p.318-326
- Abstract
- The present study was devoted to investigate the effects of the metabotropic glutamate receptor(mGluR)5 antagonist [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and the mGluR1 antagonist, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), in animal studies indicative of antiparkinsonian-like activity such as haloperidol-induced catalepsy, hypoactivity in open field following haloperidol, and rotation in rats with unilateral 6-hydroxydopamine(OHDA)-induced lesions of the midbrain dopaminergic system (alone and in combination with L-DOPA). Moreover, antidyskinetic activity of different mGluR ligands was evaluated in the rat model of L-DOPA-induced dyskinesia. Both MTEP (5 mg/kg) and EMQMCM (4... (More)
- The present study was devoted to investigate the effects of the metabotropic glutamate receptor(mGluR)5 antagonist [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and the mGluR1 antagonist, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), in animal studies indicative of antiparkinsonian-like activity such as haloperidol-induced catalepsy, hypoactivity in open field following haloperidol, and rotation in rats with unilateral 6-hydroxydopamine(OHDA)-induced lesions of the midbrain dopaminergic system (alone and in combination with L-DOPA). Moreover, antidyskinetic activity of different mGluR ligands was evaluated in the rat model of L-DOPA-induced dyskinesia. Both MTEP (5 mg/kg) and EMQMCM (4 mg/kg) slightly inhibited haloperidol (0.5 mg/kg)-induced catalepsy. However, neither substance reversed the hypoactivity produced by haloperidol (0.2 mg/kg). Although MTEP and not produce significant turning, it inhibited contralateral rotations after L-DOPA (at 5 mg/kg) and alleviated L-DOPA-induced dyskinesia (at 2.5 and 5 mg/kg) in 6-OHDA-lesioned rats. In contrast, mGluR1 antagonists EMQMCM and RS-1-aminoindan-1,5-dicarboxylic acid (AIDA) failed to modify L-DOPA-induced dyskinesia. The results of the present study suggest that either subtype of group I of mGluRs may be involved in the pathologically altered circuitry in the basal ganglia. However, the equivocal results do not strongly support the hypothesis that mGluR1 and mGluR5 antagonists may be beneficial in the symptomatic treatment of Parkinson's disease. However, mGluR5 antagonists may prove useful for the symptomatic treatment Of L-DOPA-induced dyskinesia. (c) 2006 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/414601
- author
- Dekundy, A
; Pietraszek, M
; Schaefer, D
; Cenci Nilsson, Angela
LU
and Danysz, W
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- catalepsy, turning, haloperidol, abnormal involuntary movements, in vivo
- in
- Brain Research Bulletin
- volume
- 69
- issue
- 3
- pages
- 318 - 326
- publisher
- Elsevier
- external identifiers
-
- wos:000236660900011
- pmid:16564428
- scopus:33645050113
- pmid:16564428
- ISSN
- 0361-9230
- DOI
- 10.1016/j.brainresbull.2005.12.009
- language
- English
- LU publication?
- yes
- id
- 75953c54-a82d-4b58-9b7a-d7943eea86ab (old id 414601)
- date added to LUP
- 2016-04-01 12:16:04
- date last changed
- 2022-04-05 20:06:04
@article{75953c54-a82d-4b58-9b7a-d7943eea86ab,
abstract = {{The present study was devoted to investigate the effects of the metabotropic glutamate receptor(mGluR)5 antagonist [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and the mGluR1 antagonist, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), in animal studies indicative of antiparkinsonian-like activity such as haloperidol-induced catalepsy, hypoactivity in open field following haloperidol, and rotation in rats with unilateral 6-hydroxydopamine(OHDA)-induced lesions of the midbrain dopaminergic system (alone and in combination with L-DOPA). Moreover, antidyskinetic activity of different mGluR ligands was evaluated in the rat model of L-DOPA-induced dyskinesia. Both MTEP (5 mg/kg) and EMQMCM (4 mg/kg) slightly inhibited haloperidol (0.5 mg/kg)-induced catalepsy. However, neither substance reversed the hypoactivity produced by haloperidol (0.2 mg/kg). Although MTEP and not produce significant turning, it inhibited contralateral rotations after L-DOPA (at 5 mg/kg) and alleviated L-DOPA-induced dyskinesia (at 2.5 and 5 mg/kg) in 6-OHDA-lesioned rats. In contrast, mGluR1 antagonists EMQMCM and RS-1-aminoindan-1,5-dicarboxylic acid (AIDA) failed to modify L-DOPA-induced dyskinesia. The results of the present study suggest that either subtype of group I of mGluRs may be involved in the pathologically altered circuitry in the basal ganglia. However, the equivocal results do not strongly support the hypothesis that mGluR1 and mGluR5 antagonists may be beneficial in the symptomatic treatment of Parkinson's disease. However, mGluR5 antagonists may prove useful for the symptomatic treatment Of L-DOPA-induced dyskinesia. (c) 2006 Elsevier Inc. All rights reserved.}},
author = {{Dekundy, A and Pietraszek, M and Schaefer, D and Cenci Nilsson, Angela and Danysz, W}},
issn = {{0361-9230}},
keywords = {{catalepsy; turning; haloperidol; abnormal involuntary movements; in vivo}},
language = {{eng}},
number = {{3}},
pages = {{318--326}},
publisher = {{Elsevier}},
series = {{Brain Research Bulletin}},
title = {{Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease}},
url = {{http://dx.doi.org/10.1016/j.brainresbull.2005.12.009}},
doi = {{10.1016/j.brainresbull.2005.12.009}},
volume = {{69}},
year = {{2006}},
}