Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice  

作　　者：Yan-Jiong Chen Yan-Ling Liu Qing Zhong Yan-Fang Yu Hong-Liang Su Haroldo A.Toque Yong-Hui Dang Feng Chen Ming Xu Teng Chen 

机构地区：[1]Department of Forensic Medicine,Key Laboratory of the Health Ministry for Forensic Medicine,Key Laboratory of Environment and Genes Related to Diseases,The Ministry of Education,Xi'an Jiaotong University School of Medicine,Xi'an 710061,China [2]Department of lmmunology and Pathogenic Biology,Xi'an Jiaotong University School of Medicine,Xi'an 710061,China [3]People's Procuratorate of Lanshan District,Linyi 276000,China [4]Department of Pharmacology and Vascular Biology Center,Georgia Health Sciences University,Augusta,GA 30912,USA [5]Department of Anesthesia and Critical Care,the University of Chicago,Chicago,IL 60637,USA

出　　处：《Neuroscience Bulletin》2012年第3期222-232,共11页神经科学通报（英文版）

基　　金：supported by grants from the Ministry of Science and Technology of China (2009 DFA 31080);the National Natural Science Foundation of China (30973365)

摘　　要：Objective The purpose of this study was to investigate the effect of methamphetamine （MA） on spatial learning and memory and the role of tetrahydropalmatine （THP） in MA-induced changes in these phenomena in mice. Methods Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase （ERK） in the mouse prefrontal cortex （PFC） and hippocampus. Results Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA＋THP-treated mice than in MA-treated mice. Conclusion Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.Objective The purpose of this study was to investigate the effect of methamphetamine （MA） on spatial learning and memory and the role of tetrahydropalmatine （THP） in MA-induced changes in these phenomena in mice. Methods Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase （ERK） in the mouse prefrontal cortex （PFC） and hippocampus. Results Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA＋THP-treated mice than in MA-treated mice. Conclusion Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.

关 键 词：methamphetamine tetrahydropalmatine Morris water maze ERK prefrontal cortex hippocampus drug addiction 

分 类 号：Q427[生物学—神经生物学] TQ246.31[生物学—生理学]