Objective: We set out to compare movement patterns induced by systemic administration of l-dopa versus D1- or D2-class DA receptor agonists in mice with unilateral 6-OHDA lesions of the nigrostriatal pathway.

Background: Dopamine (DA) replacement therapy in Parkinson´s disease (PD) is often initiated using DA receptor agonists, which are less dyskinesiogenic than l-dopa. Mice with unilateral 6-OHDA lesions are often used to discover new symptomatic or antidyskinetic treatments for PD, but the effects of DA agonists in this animal model have not been characterized.

Methods: Mice sustained unilateral 6-OHDA injections in the medial forebrain bundle, and were divided in three groups to receive treatment with increasing doses of skf38393, quinpirole, or l-dopa. Abnormal involuntary movements (AIMs) were rated using a validated scale. Rotational, horizontal and vertical activity was evaluated using a videotracking system returning measurements of distance travelled, rearing events, rotations, and movement speed.

Results: An overall analysis of total axial, limb and orolingual (ALO) AIM scores revealed no major differences between the three treatments: ALO AIMs had increased in a dose-dependent manner. However, when different AIM subtypes were analyzed individually, we found that quinpirole had induced a dramatic increase in axial AIMs while markedly reducing horizontal and vertical activity. By contrast, skf38393 had mainly increased orofacial AIMs and induced a large increase in horizontal and vertical activity (with a similar effect magnitude to l-dopa).

Conclusions: These results indicate that the pharmacological activation of D1 and D2 receptors activation produces strikingly different movement patterns in hemiparkinsonian mice. Their relative contribution to the genesis of dyskinesias may determine the choice of antidyskinetic treatment in the future. 

References: 10^th FENS forum of neuroscience; 2016 July 2-6; Copenhagen (Denmark).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-effects-induced-by-d1-or-d2-like-receptor-agonists-in-experimental-parkinsonism/