Luteolin inhibits behavioral sensitization by blocking methamphetamine-induced MAPK pathway activation in the caudate putamen in mice

• Published in: PloS one 2014-06, Vol.9 (6), p.e98981-e98981
• Main Authors: Yan, Tinglin, Li, Lu, Sun, Baiyu, Liu, Fei, Yang, Peng, Chen, Teng, Li, Tao, Liu, Xinshe
• Format: Article
• Language: English
• Subjects: Activation; Animals; Biology and life sciences; c-Jun protein; Cellular signal transduction; Central processing units; CPUs; Extracellular signal-regulated kinase; Forensic medicine; Hyperactivity; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Luteolin - pharmacology; Male; MAP kinase; Medicine and Health Sciences; Methamphetamine; Methamphetamine - pharmacology; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Mitogen-Activated Protein Kinases - metabolism; Motor Activity - drug effects; Neurodegeneration; Neurosciences; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Protein kinase; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Putamen; Putamen - drug effects; Putamen - metabolism; Research and Analysis Methods; Retailing; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Transcription factors; Zebrafish
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098981

To investigate the effect of luteolin on methamphetamine (MA)-induced behavioral sensitization and mitogen-activated protein kinase (MAPK) signal transduction pathway activation in mice. 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. 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. 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.