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Luteolin Inhibits Behavioral Sensitization by Blocking Methamphetamine-Induced MAPK Pathway Activation in the Caudate Putamen in Mice
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Luteolin Inhibits Behavioral Sensitization by Blocking Methamphetamine-Induced MAPK Pathway Activation in the Caudate Putamen in Mice
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Journal Article
Luteolin Inhibits Behavioral Sensitization by Blocking Methamphetamine-Induced MAPK Pathway Activation in the Caudate Putamen in Mice
2014
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Cellular signal transduction
/ CPUs
/ Extracellular signal-regulated kinase
/ JNK Mitogen-Activated Protein Kinases - metabolism
/ Kinases
/ Male
/ Medicine and Health Sciences
/ Methamphetamine - pharmacology
/ Mice
/ Mitogen-Activated Protein Kinase 1 - metabolism
/ Mitogen-Activated Protein Kinase 3 - metabolism
/ Mitogen-Activated Protein Kinases - metabolism
/ Motor Activity - drug effects
/ p38 Mitogen-Activated Protein Kinases - metabolism
/ Phosphorylation - drug effects
/ Proto-Oncogene Proteins c-fos - genetics
/ Proto-Oncogene Proteins c-fos - metabolism
/ Putamen
/ Research and Analysis Methods
/ Rodents
