Category: Neuropharmacology
Objective: We set out to compare patterns of dyskinetic behaviours induced by the systemic administration of L-DOPA and D1 or D2 receptor (D1R, D2R) agonists in mice with unilateral 6-hydroxydopamine lesions.
Background: L-DOPA-induced dyskinesia (LID) is a significant complication of dopamine replacement therapy in Parkinson´s disease (PD), and the specific role of different dopamine receptors in this disorder is poorly understood.
Method: Mice were divided in four groups to receive increasing doses of L-DOPA, a D1R agonist (SKF38393), a D2/3 agonist (quinpirole) or a selective D2R agonist (sumanirole). Axial, limb and orofacial abnormal involuntary movements (AIMs) were rated using a well-established method, while dystonic features were quantified in different body segments using a new rating scale. Automated measures of abnormal limb and trunk posturing were extracted from high-speed videos using a software for markerless pose estimation (DeepLabCut).
Results: While L-DOPA induced the full spectrum of dyskinesias, SKF38393 induced mostly orofacial and limb AIMs. By contrast, both of the D2-class agonists (quinpirole, sumanirole) induced predominantly axial AIMs. Dystonia ratings revealed that these agonists elicited marked dystonic features in trunk/neck, forelimbs, and hindlimbs, which were overall most severe in sumanirole-treated mice. Accordingly, sumanirole induced the most pronounced axial bending and hindlimb divergence in the automated video analysis. In animals treated with SKF38393, the only appreciable dystonic-like reaction consisted in sustained tail dorsiflexion and stiffness. We next compared the effects of D1R or D2R selective antagonists in L-DOPA-treatment mice, where only the D2R antagonist had a significant effect on dystonic features.
Conclusion: Taken together these results indicate that the dystonic components of LID are predominantly mediated by the D2R.
To cite this abstract in AMA style:
L. Andreoli, M. Abbaszadeh, X. Cao, A. Cenci Nilsson. Distinct patterns of dyskinetic and dystonic features following D1 or D2 receptor stimulation in a mouse model of parkinsonism [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/distinct-patterns-of-dyskinetic-and-dystonic-features-following-d1-or-d2-receptor-stimulation-in-a-mouse-model-of-parkinsonism/. Accessed May 13, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/distinct-patterns-of-dyskinetic-and-dystonic-features-following-d1-or-d2-receptor-stimulation-in-a-mouse-model-of-parkinsonism/