Phosphoinositide 3-kinase dependent modulation of morphine versus cocaine dependence involves activation of nischarin  

作　　者：LI Shuo WANG Zhi-yuan LI Fei LI Jin 

机构地区：[1]Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

出　　处：《中国药理学与毒理学杂志》2018年第9期717-718,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China (81673409).

摘　　要：OBJECTIVE Phosphoinositide 3-kinase(PI3K) activation was reported to participate in the development of effect of some drugs,such as morphine and cocaine dependence.We previous found nischarin is associated with the activation of PI3K.It is our great interest to investigate the involvement of nischarin in PI3K dependent modulation of morphine versus cocaine dependence.METHODS In order to study the role of nischarin in drug dependence and tolerance,nischarin knockout mice were used for our research.Effect of psychological dependence was studied by conditioned place preference(CPP),and the effect of physical dependence was tested by naloxone-precipitated withdrawal signs.Some brain tissues were harvested 24 h after the behavioral experiment for the further measurement.RESULTS PI3K specific inhibitor LY294002 significantly blocked the acquisition of morphine-induced CPP in wild-type mice,but had no effect on its expression.In comparison,LY294002 failed to block the acquisition of cocaine-induced CPP but inhibited the expression.Furthermore,we found naloxoneprecipitated withdrawal signs in the morphine dependent mice was inhibited by LY294002.Nischarin knockout in mice could abolish the effect of LY294002 on blocking the effects of morphine,but had no effect on cocaine.CONCLUSION PI3K activation is involved in the different phases of morphine and cocaine dependence,and nischarin plays an important role in the process.OBJECTIVE Phosphoinositide 3-kinase(PI3K) activation was reported to participate in the development of effect of some drugs,such as morphine and cocaine dependence.We previous found nischarin is associated with the activation of PI3K.It is our great interest to investigate the involvement of nischarin in PI3K dependent modulation of morphine versus cocaine dependence.METHODS In order to study the role of nischarin in drug dependence and tolerance,nischarin knockout mice were used for our research.Effect of psychological dependence was studied by conditioned place preference(CPP),and the effect of physical dependence was tested by naloxone-precipitated withdrawal signs.Some brain tissues were harvested 24 h after the behavioral experiment for the further measurement.RESULTS PI3K specific inhibitor LY294002 significantly blocked the acquisition of morphine-induced CPP in wild-type mice,but had no effect on its expression.In comparison,LY294002 failed to block the acquisition of cocaine-induced CPP but inhibited the expression.Furthermore,we found naloxoneprecipitated withdrawal signs in the morphine dependent mice was inhibited by LY294002.Nischarin knockout in mice could abolish the effect of LY294002 on blocking the effects of morphine,but had no effect on cocaine.CONCLUSION PI3K activation is involved in the different phases of morphine and cocaine dependence,and nischarin plays an important role in the process.

关 键 词：MORPHINE COCAINE PHOSPHOINOSITIDE 3-kinase 

分 类 号：R[医药卫生]