Effect of ketamine on learning and memory function and the activity of glycogen synthase kinase in hippocampal neurons of young rats

Objective:To investigate the effect of ketamine by intraperitoneal injection on the learning and memory function and the activity of glycogen synthase kinase(GSK-3β) in hippocampal neurons of young rats.Methods:Forty male SD rats of one-month age were randomly divided into groups(n=10) of administration of ketamine for 4 days(K4)or 21 days(K21),control 1(C4)and 2(C21).Group K4 and K21 received intraperitoneal injection of ketamine with initial dose of 40 mg/kg followed by administering half of the dose every 15 minutes with three times in all.Group C4 and C21 were given the equal amount of normal saline.After the injection on day 1,2,3,4,18,19,20 and 21,the rats in the four groups underwent testing the learning and memory function with Morris water maze(MWM) and were decapitated in one hour of the final test to take the hippocampus for detecting the content of GSK-3β.Results:The escape latency of the rats in group K4 delayed significantly as compared with group C4(P0.01).The activity of GSK-3β increased much higher in hippocampal neurons in K4 than that of C4,but there was no difference between group K21 and C21.No abnormal changes in the hippocampal neurons of the four groups were found under the light microscope.Conclusion:The transient learning and memory disturbance induced by intraperitoneal injection of ketamine may be related to the increased activity of GSK-3 β in hippocampal neurons.