title: Luteolin inhibits behavioral sensitization by blocking methamphetamine-induced MAPK pathway activation in the caudate putamen in mice.
abstract: OBJECTIVE
  To investigate the effect of luteolin on methamphetamine (MA)-induced behavioral sensitization and mitogen-activated protein kinase (MAPK) signal transduction pathway activation in mice.
  
  
  METHODS
  Mice received a single dose of MA to induce hyperactivity or repeated intermittent intraperitoneal injections of MA to establish an MA-induced behavioral sensitization mouse model. The effect of luteolin on the development and expression of MA-induced hyperactivity and behavioral sensitization was examined. The expression and activity of ΔFosB and the levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), phosphorylated c-Jun N-terminal kinase (pJNK), and phosphorylated p38 mitogen-activated protein kinase (pp38) in the caudate putamen (CPu) were measured by western blot.
  
  
  RESULTS
  Luteolin significantly decreased hyperactivity as well as the development and expression of MA-induced behavioral sensitization in mice. ΔFosB, pERK1/2, and pJNK levels in the CPu were higher in MA-treated mice than in control mice, whereas the pp38 level did not change. Injection of luteolin inhibited the MA-induced increase in ΔFosB, pERK1/2, and pJNK levels, but did not affect the pp38 level.
  
  
  CONCLUSIONS
  Luteolin inhibits MA-induced hyperactivity and behavioral sensitization in mice through the ERK1/2/ΔFosB pathway. Furthermore, the JNK signaling pathway might be involved in MA-induced neurodegeneration in the CPu, and luteolin inhibits this process.
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Tinglin
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Baiyu
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Shaanxi, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Shaanxi, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Shaanxi, PR China.
authors.forename: Xinshe
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D047311:Luteolin