Striatal RGS4 levels were modulated by DA depletion and L-Dopa treatment
To investigate whether RGS4 inhibition corrects a plastic adaptation of RGS4 occurring as a consequence of DA depletion and/or L-Dopa administration (Geurts et al. , 2003; Ko et al. , 2014), RGS4 levels were measured by Western analysis in the striatum of naïve, L-Dopa naïve 6-OHDA hemilesioned and dyskinetic rats (Fig. 8). In dyskinetic rats, RGS4 levels were measured both ON and OFF L-Dopa. The specificity of the antibody used was first confirmed in RGS4 knockout mice (Supp Fig. 1). ANOVA revealed a strong effect of treatment (F7,46=7.95). A marked decrease in RGS4 protein levels was found in both the lesioned (-64%) and unlesioned (-51%) striatum of 6-OHDA animals, when compared with respective naïve counterparts (Fig. 8A). If RGS4 levels were expressed as lesioned-to-unlesioned ratio, a significant reduction was detected in 6-OHDA hemilesioned rats compared to naive rats (H3,20=13.73) (Fig.8B). Chronic L-Dopa (OFF group) normalized the ratio. However, acute L-Dopa (ON group) reversed it, causing a 44% increase of RGS4 levels in the lesioned striatum. This suggests that RGS4 is rapidly upregulated in the lesioned striatum of dyskinetic animals following acute stimulation of aberrant D1 receptor signaling by L-Dopa.