BACKGROUND: So far,the progression of Alzheimers disease (AD) is not able to be halted by any drug.So more and more studies focus on the pathogenesis of AD.Evidences have shown that mGluR2/3 might play an important role in the pathogenetic process of OBJECTIVE: The purpose of the study is to observe the changes of expression of phosphorylation of ERK1/2 proteins in Alzheimers disease,investigate the effects of inhibiting metabotropic glutamate receptor2/3 on these changes,and determine the role of ERKs in pathogenesis of Alzheimers disease via metabotropic glutamate receptor2/3 pathway in vivo.DESIGN,TIME AND SETTING: A randomized,controlled,animal experiment was performed at the department of Pathophysiology,Institute of Basic Medicine,Hebei Medical University,from September 2003 to August 2009.MATERIALS:METHODS: Fifty-four Wistar rats were used.The model of Alzheimers disease was induced by administration of Aβ25~35 via left lateral cerebral ventricle.Total ERK1/2 proteins and phospho-ERK1/2 in the hippocampal CA1 region were assayed with Western immunoblot.MAIN OUTCOME MEASURES:RESULTS: Total ERK1/2 proteins in AD group showed no change.While the level ofphospho-ERK1/2 increased obviously in AD group than that in sham group (P<0.01).When animals were pretreated with α-methyl-(4-tetrazolyl-phenyl) glycine (MTPG),an inhibitor of metabotropic glutamate receptor2/3,1 week after AD model,the level of phospho-ERK1/2 increased obviously lower compared with those in animals untreated with MTPG at corresponding time points(P<0.01),which indicated that phosphorylation of ERK 1/2 normally induced in AD was blocked apparently by the administration of MTPG.CONCLUSION: The results suggested that phosphorylation of ERK1/2,rather than synthesis of ERK1/2 proteins,was promoted in AD,and that the promotion was partly mediated by metabotropic glutamate receptor2/3.