关键词: 幼鼠, 氯胺酮, LY354740, 认知功能, 促炎因子

Abstract: ［Abstract］ Objective To investigate the effects of LY354740 pretreatment on the learning and memory impairment induced by chronic ketamine exposure in juvenile mice. Methods Forty?eight healthy male C57BL/6 mice（weighed 22?32 g）were randomized into three groups：normal saline group （group NS）, ketamine group（group Ket）, LY354740 pretreatment group（group LY）. In group Ket and group LY, ketamine（per 30 mg/kg）was injected intraperitoneally three times a day at 30?minute intervals for 5 consecutive days, while in Group LY, LY354740 was injected intraperitoneally（per 15 mg/kg）30 minutes before the first injection of ketamine every day. While in group NS inject same normal saline. Cognitive test including Morris water maze and Openfield test was carried out 24 hours after the last administration of ketamine. Mice in each group were sacrificed immediately after the test and hippocampi were harvested to determine the expression of inflammatory cytokines including IL?6, IL?1 and TNF?α using ELISA. Results Compared to group NS, the escape latency was prolonged；the time in the original platform and central area in Openfield were decreased, the frequency of crossing the original platform was decreased；the levels of hippocampal IL?1, IL?6, TNF?α were increased in group Ket（P<0.05）. While in group LY, there were no significant differences of above indexes（P>0.05）. Compared to group Ket, in group LY the escape latency was significantly shortened；the time in the original platform and central area in Openfield were prolonged；the frequency of crossing the original platform was increased；the levels of hippocampal IL?1, IL?6, TNF?α were decreased（P<0.05）. Conclusion Cognitive dysfunction induced by chronic ketamine exposure can be reversed by LY354740 pretreatment in juvenile mice, which may be associated with the down?regulation of the excessive release of hippocampal cytokines.

Key words: cognitive function, inflammatory cytokines, LY354740, immature mice, ketamine