Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Parkinsons Dis. 2011;1(4):339-46. doi: 10.3233/JPD-2011-11066.
Group III metabotropic glutamate (mGlu) receptors modulate glutamatergic and GABAergic transmission in the basal ganglia. In this study, we examined a novel orthosteric agonist at the mGlu4 receptor, LSP1-2111, for its ability to affect L-DOPA-induced dyskinesia (LID), in a mouse model. In 6-OHDA-lesioned mice treated with L-DOPA, chronic co-administration of LSP1-2111 significantly attenuated the development of abnormal involuntary movements, which are regarded as a marker of dyskinesia. In contrast, a single injection of LSP1-2111 did not modify the expression of LID, once this condition had been established by previous administration of L-DOPA. LSP1-2111 did not affect L-DOPA-induced cAMP and extracellular signal-regulated protein kinase signaling, which have been previoulsy implicated in dyskinesia. These results indicate that co-administration of LSP1-2111 may improve the efficacy of standard L-DOPA therapy by attenuating its liability for dyskinesia.
III 组代谢型谷氨酸（mGlu）受体调节基底神经节中的谷氨酸能和 GABA 能传递。在这项研究中，我们研究了 mGlu4 受体的新型正构激动剂 LSP1-2111，以评估其在小鼠模型中对左旋多巴诱导的异动症（LID）的影响。在接受 L-DOPA 治疗的 6-OHDA 损伤小鼠中，LSP1-2111 的慢性共同给药显著减轻了异常不自主运动的发展，这些运动被认为是异动症的标志物。相比之下，单次注射 LSP1-2111 不会改变 LID 的表达，因为之前给予 L-DOPA 已经建立了这种情况。LSP1-2111 不影响 L-DOPA 诱导的 cAMP 和细胞外信号调节蛋白激酶信号转导，这些信号转导先前与异动症有关。这些结果表明，LSP1-2111 的共同给药可能通过减轻其异动症的易感性来改善标准 L-DOPA 治疗的疗效。
