Objective · To investigate the role of group I metabotropic glutamate receptor (mGluR) in the regulation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic plasticity in low dose ketamine protecting learning and memory function after modified electroconvulsive shock (MECS). Methods · The 2-3-month-old Sprague Dawley (SD) rats were used to establish depression models with chronic unpredicmild stress. Ten healthy rats were used as the control group (group C), and another 30 depressed rats were randomly divided into group D, group M, and group KM. Group C was not treated, group D was treated with pseudo-MECS after intraperitoneal injection of normal saline, group M was given intraperitoneal injection of propofol, and group KM was given intraperitoneal injection of propofol combined with low-dose ketamine (10 mg/kg). Both group M and group KM underwent MECS. The sucrose preference test was used to evaluate the depression status. The Morris water maze was used to detect the spatial learning and memory function. The of NMDAR1, mGluR1 and mGluR5 proteins in the hippocampus was detectedWestern blotting. Another 36 depressed rats were randomly divided into 6 groups: group DE, group m1E, group m5E, group DE, group m1E, and group m5E. Group DE and group DE were perfused with artificial cerebrospinal fluid alone. Group m1E and group m1E were perfused with artificial cerebrospinal fluid containing mGluR1 blocker. Group m5E and group m5E were perfused with artificial cerebrospinal fluid containing mGluR5 blocker. Long-term potentiations (LTP) were detected in group DE, group m1E, and group m5E. NMDAR-mediated field potentials (fEPSPNMDAR) were detected in group DE, group m1E, and group m5E. Results · After treatment, the sucrose preference percentages of group M and group KM increased compared with group D (PPPPPPPPNMDAR of group m1E and group m5E decreased (PConclusion · Ketamine up-regulates NMDAR1 and group ⅠmGluR to enhance the activation of NMDAR in the hippocampus which may be responsible for the protective effects on spatial learning and memory function in depression rats undergoing MECS.