氯胺酮对幼龄小鼠自主活动的影响和致遗忘作用及其与GABA_A、NMDA受体的关系  

Effects on Spontaneous Motor Activity and Amnestic Effect of Ketamine and Its Relationships with GABAA and NMDA Receptors in Young Mice

作　　者：高艳[1] 赵佳佳[1] 陈雪[1] 高震[1] 李伟[1] 傅焓[1] 张科学[1] 戴体俊[1] 王红军[1] 张洋[1] 

机构地区：[1]徐州医学院麻醉学院,江苏徐州221002

出　　处：《中国药房》2013年第1期27-29,共3页China Pharmacy

基　　金：国家自然科学基金资助项目(No.30872432;30471657;39970715);江苏省自然科学基金资助项目(No.BK200143)

摘　　要：目的:观察氯胺酮对幼龄小鼠自主活动和遗忘作用的影响,探讨其与γ-氨基丁酸A(GABAA)、N-甲基-D-天冬氨酸(NMDA)受体的关系。方法:将幼龄小鼠均分为3大组分别用于自主活动、避暗和跳台实验,每大组再各分为8小组(n=10):A组[生理盐水(NS)+人工脑脊液(aCSF)]、B组(氯胺酮+aCSF)、C组和D组[NS+GABAA受体特异性阻滞药荷包牡丹碱(Bic)0.10、0.20mg/kg]、E组和F组(氯胺酮+Bic0.10、0.20mg/kg)、G组(NS+NMDA60ng)、H组(氯胺酮+NMDA60ng);氯胺酮100mg/kg或NS于测试前20min腹腔注射,aCSF或Bic或NMDA于测试前5min侧脑室注射。以5min内自主活动次数评估各组小鼠自主活动,以避暗和跳台实验测定的避暗潜伏期、跳台潜伏期和错误次数评估小鼠训练后48h内的遗忘指标。结果:与A组比较,B组、E组、F组、H组小鼠自主活动次数均明显增加(P<0.05或P<0.01);与B组比较,C组、D组小鼠自主活动次数均明显减少(P<0.05或P<0.01)。避暗和跳台实验中,训练后24h与A组比较,B组、E组、F组小鼠的错误次数均明显增加,潜伏期均明显减少;与B组比较,C组、D组、G组、H组小鼠的错误次数均明显减少、潜伏期均明显增加(P<0.05或P<0.01)。训练后48h时各组间上述指标均无明显差异。结论:氯胺酮可致幼年小鼠自主活动次数增加且有显著致遗忘作用;NMDA受体是氯胺酮致遗忘作用的重要靶位,而GABAA受体则不是。OBJECTIVE：To investigate the effects of ketamine（Ket）on spontaneous motor activity and amnestic effect of Ket and its relationships with γ-aminobutyric acid（GABAA）and N-methyl-D-aspartic acid（NMDA）receptor in young mice.METHODS：Young mice were divided into 3 groups for spontaneous motor activity test,step-through test and step-down test.Every group was subdivided into 8 subgroups（n=10）,i.e.group A（NS＋aCSF）,group B（Ket＋aCSF）,group C and D [NS＋GABAA receptor specific blocker bicuculline（Bic）0.10 and 0.20 mg/kg],group E and F（Ket＋Bic 0.10 and 0.20 mg/kg）,group G（NS＋ NMDA 60 ng）,group H（Ket＋NMDA 60 ng）.Intraperitoneal injection of Ket 100 mg/kg or NS were given 20 min before test,and intralateroventricular injection of aCSF,Bic or NMDA were given 5 min before test.The spontaneous motor activities of mice were evaluated by spontaneous motor activity times（SMATs）within 5 min,and the amnestic effect of mice in 48 h after training was evaluated by error times（ETs）,step-through latency（STL）and step-down latency（SDL）.RESULTS：Compared with group A,SMATs increased significantly in group B,E,F,and H（P0.05 or P0.01）.Compared with group B,SMATs decreased significantly in group C and D（P0.05 or P0.01）.Compared with group A at 24 h after training,ETs increased in group B,E and F while STL and SDL decreased significantly in step-through test and step-down test;compared with group B,ETs decreased in group C,D,G and H while STL and SDL increased significantly（P0.05 or P0.01）.Above index had no significant difference among those groups at 48 h after training.CONCLUSIONS：Ket can increase the SMATs and have amnestic effect in young mice.NMDA receptor but not GABAA receptor may be an important target for the amnestic effect in young mice induced by Ket.

关 键 词：氯胺酮 幼龄小鼠 荷包牡丹碱 γ-氨基丁酸A N-甲基-D-天冬氨酸 自主活动 遗忘作用 

分 类 号：R965[医药卫生—药理学] R971.2[医药卫生—药学]