title: L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway.
abstract: 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 conditioned 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 (DHβE). 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 α(4), β(2) and α(7) nicotine acetylcholine receptor (nAChR) subunits induced by nicotine 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.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Di
authors.forename: Jingqi
authors.initials: J
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Chang
authors.forename: Baolu
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003214:Conditioning, Classical; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005971:Glutamates / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009042:Motivation; D009538:Nicotine / Q000494:pharmacology*; D034741:RNA, Small Interfering; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D005971:Glutamates; D034741:RNA, Small Interfering; D011978:Receptors, Nicotinic; D009538:Nicotine; C026166:theanine; D004298:Dopamine