Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease
Development of L-DOPA-induced dyskinesia (LID) remains a major problem in the long-term treatment of Parkinson's disease (PD). Sensitization to L-DOPA correlates with ectopic expression of D3 dopamine receptors in the striatum, implicating D3 receptors in development of LID.We demonstrate that...
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doaj-8bdec3277a6b42d293ed9ac154b6e5b12021-03-20T04:56:54ZengElsevierNeurobiology of Disease1095-953X2009-08-01352184192Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's diseaseNaomi P. Visanji0Susan H. Fox1Tom Johnston2Gabriela Reyes3Mark J. Millan4Jonathan M. Brotchie5Toronto Western Research Institute, 399 Bathurst Street, MC11-419, Toronto, Ontario, Canada M5T 2S8Toronto Western Research Institute, 399 Bathurst Street, MC11-419, Toronto, Ontario, Canada M5T 2S8Toronto Western Research Institute, 399 Bathurst Street, MC11-419, Toronto, Ontario, Canada M5T 2S8Toronto Western Research Institute, 399 Bathurst Street, MC11-419, Toronto, Ontario, Canada M5T 2S8Department of Psychopharmacology IDR Servier, 78290, Croissy-sur-Seine, Paris, FranceToronto Western Research Institute, 399 Bathurst Street, MC11-419, Toronto, Ontario, Canada M5T 2S8; Corresponding author. Fax: +1 4166035447.Development of L-DOPA-induced dyskinesia (LID) remains a major problem in the long-term treatment of Parkinson's disease (PD). Sensitization to L-DOPA correlates with ectopic expression of D3 dopamine receptors in the striatum, implicating D3 receptors in development of LID.We demonstrate that the selective D3 antagonist S33084 abolishes development of LID over 30 days in MPTP-lesioned marmosets without effecting the anti-parkinsonian actions of L-DOPA. Furthermore, following a 14 day washout, when challenged with L-DOPA in the absence of S33084, these animals continued to exhibit reduced LID. In the 6-OHDA-lesioned rat, S33084 similarly attenuated development of behavioural sensitization to L-DOPA. Additionally, L-DOPA–induced elevations in striatal pre-proenkephalin-A (PPE-A) (but not PPE-B, phospho[Thr34]DARPP-32, D1, and D2 receptor mRNA or D3 receptor levels) were reduced in S33084 treated animals.Our data suggest a role for D3 receptors in the development of LID and suggest that initiating L-DOPA treatment with a D3 antagonist may reduce the development of LID in PD.http://www.sciencedirect.com/science/article/pii/S0969996108002994MPTP lesioned marmoset6-hydroxydopamine lesioned ratS33084Behavioural sensitization |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naomi P. Visanji Susan H. Fox Tom Johnston Gabriela Reyes Mark J. Millan Jonathan M. Brotchie |
spellingShingle |
Naomi P. Visanji Susan H. Fox Tom Johnston Gabriela Reyes Mark J. Millan Jonathan M. Brotchie Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease Neurobiology of Disease MPTP lesioned marmoset 6-hydroxydopamine lesioned rat S33084 Behavioural sensitization |
author_facet |
Naomi P. Visanji Susan H. Fox Tom Johnston Gabriela Reyes Mark J. Millan Jonathan M. Brotchie |
author_sort |
Naomi P. Visanji |
title |
Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease |
title_short |
Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease |
title_full |
Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease |
title_fullStr |
Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease |
title_full_unstemmed |
Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease |
title_sort |
dopamine d3 receptor stimulation underlies the development of l-dopa-induced dyskinesia in animal models of parkinson's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2009-08-01 |
description |
Development of L-DOPA-induced dyskinesia (LID) remains a major problem in the long-term treatment of Parkinson's disease (PD). Sensitization to L-DOPA correlates with ectopic expression of D3 dopamine receptors in the striatum, implicating D3 receptors in development of LID.We demonstrate that the selective D3 antagonist S33084 abolishes development of LID over 30 days in MPTP-lesioned marmosets without effecting the anti-parkinsonian actions of L-DOPA. Furthermore, following a 14 day washout, when challenged with L-DOPA in the absence of S33084, these animals continued to exhibit reduced LID. In the 6-OHDA-lesioned rat, S33084 similarly attenuated development of behavioural sensitization to L-DOPA. Additionally, L-DOPA–induced elevations in striatal pre-proenkephalin-A (PPE-A) (but not PPE-B, phospho[Thr34]DARPP-32, D1, and D2 receptor mRNA or D3 receptor levels) were reduced in S33084 treated animals.Our data suggest a role for D3 receptors in the development of LID and suggest that initiating L-DOPA treatment with a D3 antagonist may reduce the development of LID in PD. |
topic |
MPTP lesioned marmoset 6-hydroxydopamine lesioned rat S33084 Behavioural sensitization |
url |
http://www.sciencedirect.com/science/article/pii/S0969996108002994 |
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