L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway  

作　　者：DI XiaoJing YAN JingQi ZHAO Yan CHANG YanZhong ZHAO BaoLu 

机构地区：[1]State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2]Department of Food Sciences and Technology, Harbin Institute of Technology at Weihai, Weihai 264209, China [3]Institute of Molecular Neurobiology, Hebei Normal University, Shijiazhuang 050016, China

出　　处：《Science China(Life Sciences)》2012年第12期1064-1074,共11页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (Grant No. 30870587);National Basic Research Program of China from the Department of Science and Technology of China(Grant No. 2006CB500700)

摘　　要：In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a con- ditioned place preference （CPP） model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine （DHI3E）. Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly in- hibited nicotine-induced tyrosine hydroxylase （TH） expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the ~4,132 and c^7 nicotine acetylcholine receptor （nAChR） subunits induced by nico- tine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of to- bacco addiction.In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a con- ditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DH E). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the 4, 2 and 7 nicotine acetylcholine receptor (nAChR) subunits induced by nico- tine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction.

关 键 词：nicotine addiction L-THEANINE nicotine acetylcholine receptor （nAChR） DOPAMINE conditioned place preference （CPP） 

分 类 号：Q42[生物学—神经生物学] TQ460.34[生物学—生理学]