Effects of repeated ketamine administration on trace fear memory and associated expression of MAPK (Mitogen-activated protein kinase)

• Main Authors: Shaw-nong Wang, 王少農
• Other Authors: Ingrid Y.-C, Liu
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/03486999356750829366

碩士 === 慈濟大學 === 神經科學研究所 === 94 === Recent studies have shown that trace fear conditioning (TFC) was hippocampal dependent. Mice were followed the trace fear conditioning to learn the connection between the conditioned stimulus (CS) and unconditioned stimulus (US) . Previous studies have shown that the trace fear conditioning would evoke expression of learning and memory associated proteins, such us Erk (Extracellular Signal-Reagulated kinase). Ketamine is an NMDA receptor antagonist, it would block the NMDA receptor channel, supress Erk signaling and LTP formation, in turn cause memory defection. We suspect that repeated ketamine administration would influence the phosphorylation of Erk and p38 proteins. Therefore, We injected ketamine into mice that learned trace fear conditioning and investigated their freezing to cues and associated phosphorylation of Erk and p38. After the trace fear conditioning, mice received ketamine administration for 7 continuous days with different dosages (25 mg/kg, 50 mg/kg, 100 mg/kg), and then tested them on contextual and tone memory. We found that their freezing behavior was decreased to both contextual and tone test. In addition, Erk1 phosphorylation was decreased in the prefrontal cortex after tone test in 100 mg/kg group. In the hippocampus, Erk1 was also decresed in the 50 mg/kg group, but changes of p38 phosphorylation was not significant after both contextual test and tone test. Future works will focus on investigating changes of upstream and downstream molecules of Erk1 signaling after tone test to elucidate the underlying molecular mechanism of ketamine effect on retrieval of trace fear memory.