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Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia.
Mov Disord. 2023 03; 38(3):410-422.MD

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 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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Espa E
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Song L
Department of Neurology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Skovgård K
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Fanni S
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Cenci MA
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

MeSH

RatsAnimalsLevodopaDopamine AgonistsAntiparkinson AgentsRats, Sprague-DawleyDyskinesia, Drug-InducedOxidopamineDisease Models, Animal

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

36656044

Citation

Espa, Elena, et al. "Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 38, no. 3, 2023, pp. 410-422.
Espa E, Song L, Skovgård K, et al. Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia. Mov Disord. 2023;38(3):410-422.
Espa, E., Song, L., Skovgård, K., Fanni, S., & Cenci, M. A. (2023). Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia. Movement Disorders : Official Journal of the Movement Disorder Society, 38(3), 410-422. https://doi.org/10.1002/mds.29301
Espa E, et al. Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia. Mov Disord. 2023;38(3):410-422. PubMed PMID: 36656044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia. AU - Espa,Elena, AU - Song,Lu, AU - Skovgård,Katrine, AU - Fanni,Silvia, AU - Cenci,M Angela, Y1 - 2023/01/19/ PY - 2022/11/17/revised PY - 2022/09/23/received PY - 2022/12/05/accepted PY - 2023/1/20/pubmed PY - 2023/3/23/medline PY - 2023/1/19/entrez KW - Parkinson's disease KW - animal models of L-dopa-induced dyskinesia KW - antidyskinetic treatments KW - ropinirole SP - 410 EP - 422 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 38 IS - 3 N2 - 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. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/36656044/Dopamine_Agonist_Cotreatment_Alters_Neuroplasticity_and_Pharmacology_of_Levodopa_Induced_Dyskinesia_ DB - PRIME DP - Unbound Medicine ER -