Objective To investigate the effects of metabotropic glutamate receptor 5 antagonist methyl-6-ethynyl-pyridine (MPEP) on behavior and striatal postsynaptic density-95 (PSD-95) protein expression changes in rats with levodopa-induced dyskinesia (LID).Methods Hemi-parkinsonian rat models were established by stereotaxically injection of 6-hydroxy dopamine (6-OHDA) in the right medial forebrain bundle;then,these 32 Parkinson's disease (PD) rats were randomly divided into four groups (n=8):levodopa (L-DOPA) treatment group,receiving L-DOPA 25 mg/kg+benserazide 6.25 mg/kg;saline group,giving the same volume of saline;MPEP treatment group,receiving 1.5 mg/kg MPEP;and L-DOPA+MPEP treatment group,accepted L-DOPA 25 mg/kg+benserazide 6.25 mg/kg+MPEP 1.5 mg/kg;All rats received intraperitoneal injections twice daily and continued for 21 days.At days 2,9,11,18 and 21,behavior changes of all rats were detected;the protein and mRNA levels of PSD-95 in striatal tissues were detected by Western blotting and real-time PCR,respectively.Results (1) Abnormal involuntary movement scores were significantly decreased in rats of L-DOPA+MPEP treatment group (42.33±12.43,41.80±13.69 and 40.30±9.76) as compared with those in L-DOPA treatment group (55.56±9.28,54.89±7.01 and 58.44±7.68) on days 11,18,and 21 (P＜0.05).Forepaw adjusting steps were significantly increased in Parkinson rats of L-DOPA+MPEP treatment group as compared with rats of L-DOPA treatment group (P＜0.05);and the increased extent was not decreased as time prolonging.Forepaw adjusting steps were also increased after MPEP treatment alone.Co-administration of L-DOPA with MPEP reversed the shortening of rotational response duration induced by L-DOPA.(2) The up-regulation of PSD-95 protein and mRNA levels in the lesioned striatum was noted in the L-DOPA treatment group (1.39 ±0.37 and 3.80 ±1.09),while this trend could be alleviated by coadministration of L-DOPA with MPEP (0.76±0.66 and 1.65±0.81).Conclusion MPEP can alleviate abnormal involuntary movements induced by L-DOPA and strengthen the anti-parkinsonian effect of L-DOPA,which may be related to regulation of striatal PSD-95 expression induced by L-DOPA.