Overexpression of RGS protein genes in striatal sensorimotor regions correlates to motor complications in the L-DOPA-induced dyskinetic rat model of Parkinson’s disease

Daniel Ko, Alan Crossman, Paula Ravenscroft. 1The University of Manchester, Manchester, United Kingdom, 2Motac Neuroscience, Manchester, United Kingdom.

The dopamine precursor, L-3-4-dihydroxyphenylalanine (L-DOPA), is the most effective symptomatic treatment of Parkinson’s disease (PD). However, long-term treatment leads to severe side effects such as abnormal involuntary movements (AIMs). This may be due to abnormal pulsatile dopamine receptor stimulation of L-DOPA. Regulators of G-protein signalling (RGS) proteins negatively modulate dopamine receptor signalling and may have functional roles in LID.

Rats received unilateral 6-OHDA lesions of the right medial forebrain bundle. L-DOPA and benserazaide (6 and 15 mg/kg, respectively) were administered daily for 21 days to induce AIMs. RGS2 and RGS4 expression was measured by in situ hybridisation.

RGS2 and RGS4 mRNA levels were increased (89% ventrolateral and 25% dorsolateral, respectively) in the 6-OHDA-lesioned striatum following L-DOPA treatment. Moreover, increased RGS4 mRNA levels were specific to sensorimotor regions and positively correlated to AIMs severity (r= 0.6244).

These data suggest that RGS proteins may have a functional role in LID and may prove to be a future therapeutic target.