Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia

Abstract

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with l-DOPA. However, long-term l-DOPA use may cause dyskinesia. Although the pathogenic mechanism of l-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i) develop and standardise an experimental model of l-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii) evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-hydroxydopamine (6-OHDA)), and dyskinetic rats (injected with l-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (P<.05). All AIMs were significantly evident from day 5 and persisted until the last day of injection. D2R density was greater in the striatum and the medial anterior brain of the lesioned and dyskinetic rats than in those of controls. Our results suggest an association between D2R expression and locomotor AIMs. We conclude that RD2 is involved in l-DOPA-induced dyskinesia.