Group II metabotropic glutamate receptors (mGlu_2/3 receptors) have been regarded as promising candidates for the treatment of L-DOPA-induced dyskinesia (LID); however, confirmation is still lacking. As the hub of the basal ganglia circuit, the striatum plays a critical role in action control. Supersensitive responsiveness of glutamatergic corticostriatal input may be the key mechanism for the development of LID. In this study, we first examined the potency of LY354740 (12 mg/kg, i.p.) in modulating glutamate and dopamine release in lesioned striatum of stable LID rats. Then, we injected LY354740 (20nmoL or 40nmoL in 4 μL of sterile 0.9 % saline) directly into the lesioned striatum to verify its ability to reduce or attenuate L-DOPA-induced abnormal involuntary movements. In experiment conducted in established LID rats, after continuous injection for 4 days, we found that LY354740 significantly reduced the expression of dyskinesia. In another experiment conducted in parkinsonism rat models, we found that LY354740 attenuated the development of LID with an inverted-U dose–response curve. The role of LY354740 in modulating striatal expressions of LID-related molecular changes was also assessed after these behavioral experiments. We found that LY354740 significantly inhibited abnormal expressions of p-Fyn/p-NMDA/p-ERK1/2/p-HistoneH3/ΔFosB, which is in line with its ability to alleviate abnormal involuntary movements in both LID expression and induction phase. Our study indicates that activation of striatal mGlu_2/3 receptors can attenuate the development of dyskinesia in parkinsonism rats and provide some functional improvements in LID rats by inhibiting LID-related molecular changes.

II 类代谢型谷氨酸受体（mGlu _2/3受体）被认为是治疗 L-DOPA 引起的运动障碍 (LID) 的有希望的候选者；然而，仍缺乏确认。作为基底神经节回路的枢纽，纹状体在动作控制中起着至关重要的作用。谷氨酸能皮质纹状体输入的超敏反应可能是 LID 发生的关键机制。在这项研究中，我们首先检查了 LY354740（12 mg/kg，腹膜内注射）调节稳定 LID 大鼠受损纹状体中谷氨酸和多巴胺释放的效力。然后，我们将 LY354740（20nmoL 或 40nmoL，溶于 4 μL 0.9% 无菌盐水）直接注射到病变纹状体中，以验证其减少或减弱 L-DOPA 引起的异常不自主运动的能力。在已建立的LID大鼠中进行的实验中，连续注射4天后，我们发现LY354740显着减少了运动障碍的表达。在帕金森病大鼠模型中进行的另一项实验中，我们发现 LY354740 可以通过倒 U 型剂量反应曲线减弱 LID 的发展。这些行为实验后还评估了 LY354740 在调节 LID 相关分子变化的纹状体表达中的作用。我们发现LY354740显着抑制p-Fyn/p-NMDA/p-ERK1/2/p-HistoneH3/ΔFosB的异常表达，这与其在LID表达和诱导期缓解异常不自主运动的能力相符。我们的研究表明，纹状体 mGlu _2/3受体的激活可以减轻帕金森病大鼠运动障碍的发展，并通过抑制 LID 相关分子变化来改善 LID 大鼠的功能。