Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine D1/D5 receptors
Duan TT1,2; Tan JW1,3; Yuan Q1; Cao J1; Zhou QX[*]1; Xu L[*]1
刊名PSYCHOPHARMACOLOGY
2013
卷号228期号:3页码:451-461
关键词Ketamine Psychosis Hippocampus Dopamine Spatial memory Synaptic plasticity
通讯作者qixin_zhou@126.com ; lxu@vip.163.com
合作状况其它
英文摘要 Subanesthetic doses of ketamine have been reported to induce psychotic states that may mimic positive and negative symptoms as well as cognitive and memory deficits similar to those observed in schizophrenia. The cognitive and memory deficits are persistent, and their underlying cellular mechanisms remain unclear. 

We sought to investigate the roles of dopamine D1/D5 receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal synaptic transmission and spatial memory impairment induced by ketamine. 

We examined the effects of subanesthetic ketamine on hippocampal synaptic transmission in freely moving rats. Spatial memory was tested with the Morris water maze. Pretreatment with the D1/D5 receptors antagonist SCH23390 or the AMPA receptors endocytosis interfering peptide Tat-GluR2(3Y) was conducted to examine their capacities to reverse ketamine-induced electrophysiological and behavioral alterations. A series of behavioral observations, including locomotion, prepulse inhibition, and social interaction, were also conducted after ketamine treatment. 

Ketamine induced synaptic depression lasting at least 4 h at hippocampal Schaffer collateral-CA1 synapses in freely moving rats and long-term spatial memory impairment. Both the effects were blocked by either SCH23390 or Tat-GluR2(3Y). Ketamine also elicited transient behavioral changes lasting less than 90 min, such as hyperlocomotion and prepulse inhibition deficits. These changes were ameliorated by SCH23390 but not by Tat-GluR2(3Y). Rats treated with ketamine showed social withdrawal that was also attenuated by either SCH23390 or Tat-GluR2(3Y). 

Our results indicate that hippocampal synaptic depression is involved in ketamine-induced memory impairment, and this is modulated by D1/D5 receptors activation and AMPA receptors endocytosis.
收录类别SCI
资助信息This work was supported by 973 program from the Ministry of Science and Technology of China (2013CB835103 to L.X., 2009CB941302 to L.X. and 2009CB522006 to J.C.), the Strategic Prior- ity Research Program of the Chinese Academy of Science (XDB02020200to L.X.), and The National Science Foundation ofChina (31100775 to Q.-X. Z.) and NSFC-Yunnan Joint Grant (U1032605 to L.X.) and NSFC-CIHR Joint Grant (81161120536 to L.X.).
语种英语
WOS记录号WOS:000321588300011
公开日期2013-08-28
内容类型期刊论文
源URL[http://159.226.149.42:8088/handle/152453/7601]  
专题昆明动物研究所_学习记忆的分子神经机制
昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位1.Key Laboratory of Animal Models and Human Disease Mechanisms, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
2.School of Life Sciences, University of Science and Technology of China, Hefei 230026, Chi
3.University of Chinese Academy of Sciences, Beijing 100049, China
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Duan TT,Tan JW,Yuan Q,et al. Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine D1/D5 receptors[J]. PSYCHOPHARMACOLOGY,2013,228(3):451-461.
APA Duan TT,Tan JW,Yuan Q,Cao J,Zhou QX[*],&Xu L[*].(2013).Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine D1/D5 receptors.PSYCHOPHARMACOLOGY,228(3),451-461.
MLA Duan TT,et al."Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine D1/D5 receptors".PSYCHOPHARMACOLOGY 228.3(2013):451-461.
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