TY - JOUR T1 - RGS9–2 Negatively Modulates <span class="sc">l</span>-3,4-Dihydroxyphenylalanine-Induced Dyskinesia in Experimental Parkinson's Disease JF - The Journal of Neuroscience JO - J. Neurosci. SP - 14338 LP - 14348 DO - 10.1523/JNEUROSCI.4223-07.2007 VL - 27 IS - 52 AU - Stephen J. Gold AU - Chau V. Hoang AU - Bryan W. Potts AU - Gregory Porras AU - Elsa Pioli AU - Ki Woo Kim AU - Agnes Nadjar AU - Chuan Qin AU - Gerald J. LaHoste AU - Qin Li AU - Bernard H. Bioulac AU - Jeffrey L. Waugh AU - Eugenia Gurevich AU - Rachael L. Neve AU - Erwan Bezard Y1 - 2007/12/26 UR - http://www.jneurosci.org/content/27/52/14338.abstract N2 - Chronic l-dopa treatment of Parkinson's disease (PD) often leads to debilitating involuntary movements, termed l-dopa-induced dyskinesia (LID), mediated by dopamine (DA) receptors. RGS9–2 is a GTPase accelerating protein that inhibits DA D2 receptor-activated G proteins. Herein, we assess the functional role of RGS9–2 on LID. In monkeys, Western blot analysis of striatal extracts shows that RGS9–2 levels are not altered by MPTP-induced DA denervation and/or chronic l-dopa administration. In MPTP monkeys with LID, striatal RGS9–2 overexpression – achieved by viral vector injection into the striatum – diminishes the involuntary movement intensity without lessening the anti-parkinsonian effects of the D1/D2 receptor agonist l-dopa. In contrasts, in these animals, striatal RGS9–2 overexpression diminishes both the involuntary movement intensity and the anti-parkinsonian effects of the D2/D3 receptor agonist ropinirole. In unilaterally 6-OHDA-lesioned rats with LID, we show that the time course of viral vector-mediated striatal RGS9–2 overexpression parallels the time course of improvement of l-dopa-induced involuntary movements. We also find that unilateral 6-OHDA-lesioned RGS9−/− mice are more susceptible to l-dopa-induced involuntary movements than unilateral 6-OHDA-lesioned RGS9+/+ mice, albeit the rotational behavior – taken as an index of the anti-parkinsonian response – is similar between the two groups of mice. Together, these findings suggest that RGS9–2 plays a pivotal role in LID pathophysiology. However, the findings also suggest that increasing RGS9–2 expression and/or function in PD patients may only be a suitable therapeutic strategy to control involuntary movements induced by nonselective DA agonist such as l-dopa. ER -