Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia. / Correlación entre la expresión del receptor dopaminérgico D2 y presencia de movimientos involuntarios anormales (MIA) en un modelo de disquinesia en ratas Wistar hemiparkinsonizadas.

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-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.

Correlación entre la expresión del receptor dopaminérgico D2 y presencia de movimientos involuntarios anormales (MIA) en un modelo de disquinesia en ratas Wistar hemiparkinsonizadas / Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia

La enfermedad de Parkinson (EP) se caracteriza por una serie de deficiencias motoras que son tratadas comúnmente con L-DOPA; sin embargo, tras un uso crónico se desarrollan disquinesias inducidas por L-DOPA (DIL). Por otra parte, el origen de las DIL no está del todo claro, pero se asocia con alteración en receptores dopaminérgicos, donde los receptores D2 (RD2) han sido poco estudiados. El presente trabajo buscó: 1) desarrollar y estandarizar un modelo experimental de disquinesia con L-DOPA en ratas hemiparkinsonizadas, y 2) evaluar la correlación entre la expresión del RD2 y la manifestación de movimientos involuntarios anormales (MIA). Se utilizaron 21 ratas Wistar macho asignadas a 3 grupos: control intacto, lesionados (con la neurotoxina 6-OHDA) y lesionados disquinéticos (inyectados con L-DOPA durante 19 días). Los reactivos biológicos se sometieron a pruebas comportamentales para evaluar el deterioro sensoriomotor. Los animales del grupo disquinético desarrollaron de forma gradual MIA durante el tratamiento, siendo mayores los MIA de miembro anterior y menores los de tipo locomotor (p < 0,05). Todos los MIA fueron significativamente evidentes a partir del día 5 y se mantuvieron hasta el último día de inyección. Además, se pudo evidenciar incremento en la densidad del RD2 en el estriado y el cerebro anterior medial en los grupos lesionados con respecto al control, así como también una posible asociación entre la expresión del RD2 y MIA de tipo locomotor. Por lo que concluimos que el RD2 está implicado en el fenómeno disquinético generado con la L-DOPA. (AU)

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-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. (AU)