title: The mammalian target of rapamycin pathway in the basolateral amygdala is critical for nicotine-induced behavioural sensitization.
abstract: Repeated exposure to nicotine increases psychomotor activity. Long-lasting neural plasticity changes that contribute to the nicotine-induced development of locomotor sensitization have been identified. The mammalian target of rapamycin complex 1 (mTORC1) signalling pathway is involved in regulating the neuroplasticity of the central nervous system. In this study, we examined the role of mTORC1 in the amygdala in nicotine-induced locomotor sensitization. Rapamycin, an inhibitor of mTORC1, was infused into the basolateral amygdala (BLA) and central amygdala (CeA) or systemically administered to investigate the role of the mTORC1 in the development and expression of nicotine-induced locomotor sensitization. We found that locomotor activity progressively increased during the initiation of nicotine-induced locomotor sensitization and the expression of nicotine sensitization was induced by nicotine challenge injection (0.35 mg/kg s.c.) after five days of withdrawal. The initiation of nicotine-induced locomotor sensitization was accompanied by the increased phosphorylated level of mTORC1 downstream target proteins including p-p70s6k and p-4EBP in the BLA, but not CeA. Intra-BLA infusion or systemic administration of rapamycin blocked locomotor activity. Increased p-p70s6k and p-4EBP were also observed in the expression of nicotine sensitization, which was demonstrated to be inhibited by systemic rapamycin administration. Our findings indicated that mTORC1 activity in the BLA, but not the CeA, mediated the initiation and expression of nicotine-induced locomotor sensitization, and may become a potential target for the treatment of nicotine addiction.
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Peng
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Yalun
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: National Institute on Drug Dependence,Peking University,Beijing,China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Luo
authors.affiliation: National Institute on Drug Dependence,Peking University,Beijing,China.
authors.forename: Yanxue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: National Institute on Drug Dependence,Peking University,Beijing,China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: National Institute on Drug Dependence,Peking University,Beijing,China.
authors.forename: Zengbo
authors.initials: Z
authors.lastname: Ding
authors.affiliation: National Institute on Drug Dependence,Peking University,Beijing,China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University),Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan, Hubei,China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D004334:Drug Administration Schedule; D007166:Immunosuppressive Agents / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D018722:Nicotinic Agonists; D010750:Phosphoproteins; D009538:Nicotine; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus