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Role of microsomal epoxide hydrolase in methamphetamine‐induced drug dependence in mice
Author(s) -
Shin EunJoo,
Bing Guoying,
Chae Jong Seok,
Kim Tae Woo,
Bach JaeHyung,
Park Dae Hun,
Yamada Kiyofumi,
Nabeshima Toshitaka,
Kim HyoungChun
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22166
Subject(s) - meth , methamphetamine , microsomal epoxide hydrolase , nucleus accumbens , chemistry , epoxide hydrolase , extracellular , microdialysis , pharmacology , neurochemical , striatum , biochemistry , dopamine , cytochrome p450 , microsome , biology , metabolism , enzyme , endocrinology , receptor , monomer , organic chemistry , acrylate , polymer
Microsomal epoxide hydrolase (mEH) and cytochrome P‐450 (CYP) ensure the rapid detoxification of epoxides generated during the oxidative metabolism of xenobiotics. Although CYP has been demonstrated to modulate methamphetamine (METH)‐induced behavioral effects, little is known about the role of the mEH gene on these effects. We examined the role of mEH gene expression in METH‐induced conditioned place preference and behavioral sensitization by using mEH –/– and wild‐type (WT) mice. Extracellular dopamine (DA) levels and DA uptake into synaptosomes were assessed by using an in vivo microdialysis and [ 3 H]DA uptake assay. We applied double‐label immunocytochemistry to characterize mEH‐positive cellular types. METH‐induced behavioral responses paralleled striatal c‐Fos‐like immunoreactivity. METH treatment resulted in increased extracellular DA levels in the nucleus accumbens but decreased synaptosomal DA uptake in the striatum. These behavioral and neurochemical changes were more pronounced in the mEH –/– mice than in WT mice. In WT mice, mEH‐like immunoreactivity was expressed in astrocytes labeled by GFAP or S100B after METH treatment. The results suggest that epoxide intermediates mediate METH drug dependence and that astrocytic reactions of mEH protein are important in the endogenous modulation in response to METH drug dependence. © 2009 Wiley‐Liss, Inc.