The anti-dyskinetic effect of dopamine receptor blockade is enhanced in parkinsonian rats following dopamine neuron transplantation.
Shin, Eunju LU ; Lisci, Carlo LU ; Tronci, Elisabetta LU ; Fidalgo, Camino ; Stancampiano, Roberto ; Björklund, Anders LU
and Carta, Manolo
LU
(2014)
In Neurobiology of Disease
62.
p.233-240
- Abstract
- Graft-induced dyskinesia (GID) is a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. We have recently shown that DA D2 receptor blockade produces sticking blockade of dyskinesia induced by amphetamine in grafted 6-OHDA-lesioned rats, a model of GID. This study was designed to investigate whether blockade of DA D1 receptors could produce similar outcome, and to see whether the effect of these treatments in grafted rats was specific for dyskinesia induced by amphetamine, or could also influence L-DOPA-induced dyskinesia (LID). L-DOPA-primed rats received transplants of fetal DA neurons into the DA-denervated striatum. Beginning at 20weeks after transplantation rats were subjected to pharmacological... (More)
- Graft-induced dyskinesia (GID) is a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. We have recently shown that DA D2 receptor blockade produces sticking blockade of dyskinesia induced by amphetamine in grafted 6-OHDA-lesioned rats, a model of GID. This study was designed to investigate whether blockade of DA D1 receptors could produce similar outcome, and to see whether the effect of these treatments in grafted rats was specific for dyskinesia induced by amphetamine, or could also influence L-DOPA-induced dyskinesia (LID). L-DOPA-primed rats received transplants of fetal DA neurons into the DA-denervated striatum. Beginning at 20weeks after transplantation rats were subjected to pharmacological treatments with either L-DOPA (6mg/kg) or amphetamine (1.5mg/kg) alone, or in combination with the D1 receptor antagonist SCH23390, the D2 receptor antagonist eticlopride, and the 5-HT1A agonist/D2 receptor antagonist buspirone. Grafted rats developed severe GID, while LID was reduced. Both eticlopride and SCH23390 produced near-complete suppression of GID already at very low doses (0.015 and 0.1mg/kg, respectively). Buspirone induced similar suppression at a dose as low as 0.3mg/kg, which is far lower than the dose known to affect LID in non-grafted dyskinetic rats. In agreement with our previous results, the effect of buspirone was independent from 5-HT1A receptor activation, as it was not counteracted by the selective 5-HT1A antagonist WAY100635, but likely due to D2 receptor blockade. Most interestingly, the same doses of eticlopride, SCH23390 and buspirone were found to suppress LID in grafted but not in control dyskinetic rats. Taken together, these data demonstrate that the DA cell grafts strikingly exacerbate the effect of DA D1 and D2 receptor blockade against both GID and LID, and suggest that the anti-GID effect of buspirone seen in patients may also be due to blockade of DA D2 receptors. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4143204
- author
- Shin, Eunju
LU
; Lisci, Carlo
LU
; Tronci, Elisabetta
LU
; Fidalgo, Camino
; Stancampiano, Roberto
; Björklund, Anders
LU
and Carta, Manolo
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurobiology of Disease
- volume
- 62
- pages
- 233 - 240
- publisher
- Elsevier
- external identifiers
-
- pmid:24135006
- wos:000330553600021
- scopus:84886826502
- pmid:24135006
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2013.09.021
- language
- English
- LU publication?
- yes
- id
- 6e9ff93a-5578-4b90-8be5-c3261d4b788c (old id 4143204)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24135006?dopt=Abstract
- date added to LUP
- 2016-04-01 10:09:02
- date last changed
- 2022-01-25 20:14:12
@article{6e9ff93a-5578-4b90-8be5-c3261d4b788c,
abstract = {{Graft-induced dyskinesia (GID) is a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. We have recently shown that DA D2 receptor blockade produces sticking blockade of dyskinesia induced by amphetamine in grafted 6-OHDA-lesioned rats, a model of GID. This study was designed to investigate whether blockade of DA D1 receptors could produce similar outcome, and to see whether the effect of these treatments in grafted rats was specific for dyskinesia induced by amphetamine, or could also influence L-DOPA-induced dyskinesia (LID). L-DOPA-primed rats received transplants of fetal DA neurons into the DA-denervated striatum. Beginning at 20weeks after transplantation rats were subjected to pharmacological treatments with either L-DOPA (6mg/kg) or amphetamine (1.5mg/kg) alone, or in combination with the D1 receptor antagonist SCH23390, the D2 receptor antagonist eticlopride, and the 5-HT1A agonist/D2 receptor antagonist buspirone. Grafted rats developed severe GID, while LID was reduced. Both eticlopride and SCH23390 produced near-complete suppression of GID already at very low doses (0.015 and 0.1mg/kg, respectively). Buspirone induced similar suppression at a dose as low as 0.3mg/kg, which is far lower than the dose known to affect LID in non-grafted dyskinetic rats. In agreement with our previous results, the effect of buspirone was independent from 5-HT1A receptor activation, as it was not counteracted by the selective 5-HT1A antagonist WAY100635, but likely due to D2 receptor blockade. Most interestingly, the same doses of eticlopride, SCH23390 and buspirone were found to suppress LID in grafted but not in control dyskinetic rats. Taken together, these data demonstrate that the DA cell grafts strikingly exacerbate the effect of DA D1 and D2 receptor blockade against both GID and LID, and suggest that the anti-GID effect of buspirone seen in patients may also be due to blockade of DA D2 receptors.}},
author = {{Shin, Eunju and Lisci, Carlo and Tronci, Elisabetta and Fidalgo, Camino and Stancampiano, Roberto and Björklund, Anders and Carta, Manolo}},
issn = {{0969-9961}},
language = {{eng}},
pages = {{233--240}},
publisher = {{Elsevier}},
series = {{Neurobiology of Disease}},
title = {{The anti-dyskinetic effect of dopamine receptor blockade is enhanced in parkinsonian rats following dopamine neuron transplantation.}},
url = {{https://lup.lub.lu.se/search/files/1604585/4934203.pdf}},
doi = {{10.1016/j.nbd.2013.09.021}},
volume = {{62}},
year = {{2014}},
}