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Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia

Espa, Elena LU ; Song, Lu LU ; Skovgård, Katrine LU ; Fanni, Silvia LU and Cenci, M Angela LU orcid (2023) In Movement Disorders 38(3). p.410-422
Abstract

BACKGROUND: Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive combination therapies that often include dopamine agonists.

OBJECTIVE: Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses.

METHODS: Different regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug... (More)

BACKGROUND: Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive combination therapies that often include dopamine agonists.

OBJECTIVE: Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses.

METHODS: Different regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug categories were investigated in parallel groups of rats receiving either L-dopa monotreatment or L-dopa combined with ropinirole.

RESULTS: We defined chronic regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment inducing overall similar abnormal involuntary movement scores. Compared with the monotreatment group, animals receiving the L-dopa-ropinirole combination exhibited an overall lower striatal expression of ∆FosB with a distinctive compartmental distribution. The expression of angiogenesis markers and blood-brain barrier hyperpermeability was markedly reduced after L-dopa-ropinirole cotreatment compared with L-dopa monotreatment. Moreover, significant group differences were detected upon examining the response to candidate antidyskinetic drugs. In particular, compounds modulating D1 receptor signaling had a stronger effect in the L-dopa-only group, whereas both amantadine and the selective NMDA antagonist MK801 produced a markedly larger antidyskinetic effect in L-dopa-ropinirole cotreated animals.

CONCLUSIONS: Cotreatment with ropinirole altered LID-related neuroplasticity and pharmacological response profiles. The impact of adjuvant dopamine agonist treatment should be taken into consideration when investigating LID mechanisms and candidate interventions in both clinical and experimental settings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Rats, Animals, Levodopa/therapeutic use, Dopamine Agonists/pharmacology, Antiparkinson Agents/therapeutic use, Rats, Sprague-Dawley, Dyskinesia, Drug-Induced/drug therapy, Oxidopamine, Disease Models, Animal
in
Movement Disorders
volume
38
issue
3
pages
410 - 422
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85146475953
  • pmid:36656044
ISSN
0885-3185
DOI
10.1002/mds.29301
language
English
LU publication?
yes
additional info
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
id
075112a5-4de4-458a-a45f-fc18a6df65a5
date added to LUP
2023-09-19 09:28:52
date last changed
2024-04-19 01:23:58
@article{075112a5-4de4-458a-a45f-fc18a6df65a5,
  abstract     = {{<p>BACKGROUND: Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive combination therapies that often include dopamine agonists.</p><p>OBJECTIVE: Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses.</p><p>METHODS: Different regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug categories were investigated in parallel groups of rats receiving either L-dopa monotreatment or L-dopa combined with ropinirole.</p><p>RESULTS: We defined chronic regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment inducing overall similar abnormal involuntary movement scores. Compared with the monotreatment group, animals receiving the L-dopa-ropinirole combination exhibited an overall lower striatal expression of ∆FosB with a distinctive compartmental distribution. The expression of angiogenesis markers and blood-brain barrier hyperpermeability was markedly reduced after L-dopa-ropinirole cotreatment compared with L-dopa monotreatment. Moreover, significant group differences were detected upon examining the response to candidate antidyskinetic drugs. In particular, compounds modulating D1 receptor signaling had a stronger effect in the L-dopa-only group, whereas both amantadine and the selective NMDA antagonist MK801 produced a markedly larger antidyskinetic effect in L-dopa-ropinirole cotreated animals.</p><p>CONCLUSIONS: Cotreatment with ropinirole altered LID-related neuroplasticity and pharmacological response profiles. The impact of adjuvant dopamine agonist treatment should be taken into consideration when investigating LID mechanisms and candidate interventions in both clinical and experimental settings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>}},
  author       = {{Espa, Elena and Song, Lu and Skovgård, Katrine and Fanni, Silvia and Cenci, M Angela}},
  issn         = {{0885-3185}},
  keywords     = {{Rats; Animals; Levodopa/therapeutic use; Dopamine Agonists/pharmacology; Antiparkinson Agents/therapeutic use; Rats, Sprague-Dawley; Dyskinesia, Drug-Induced/drug therapy; Oxidopamine; Disease Models, Animal}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{410--422}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Movement Disorders}},
  title        = {{Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia}},
  url          = {{http://dx.doi.org/10.1002/mds.29301}},
  doi          = {{10.1002/mds.29301}},
  volume       = {{38}},
  year         = {{2023}},
}