Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence in mice

Eun Joo Shin, Guoying Bing, Jong Seok Chae, Tae Woo Kim, Jae Hyung Bach, Dae Hun Park, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung Chun Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 [3H]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.

Original languageEnglish
Pages (from-to)3679-3686
Number of pages8
JournalJournal of Neuroscience Research
Volume87
Issue number16
DOIs
Publication statusPublished - 01-12-2009
Externally publishedYes

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Epoxide Hydrolases
Methamphetamine
Substance-Related Disorders
mouse EPHX1 protein
Dopamine
Epoxy Compounds
Cytochrome P-450 Enzyme System
Corpus Striatum
Synaptosomes
Microdialysis
Nucleus Accumbens
Xenobiotics
Astrocytes
Immunohistochemistry
Gene Expression
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Shin, E. J., Bing, G., Chae, J. S., Kim, T. W., Bach, J. H., Park, D. H., ... Kim, H. C. (2009). Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence in mice. Journal of Neuroscience Research, 87(16), 3679-3686. https://doi.org/10.1002/jnr.22166
Shin, Eun Joo ; Bing, Guoying ; Chae, Jong Seok ; Kim, Tae Woo ; Bach, Jae Hyung ; Park, Dae Hun ; Yamada, Kiyofumi ; Nabeshima, Toshitaka ; Kim, Hyoung Chun. / Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence in mice. In: Journal of Neuroscience Research. 2009 ; Vol. 87, No. 16. pp. 3679-3686.
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abstract = "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 [3H]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.",
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Shin, EJ, Bing, G, Chae, JS, Kim, TW, Bach, JH, Park, DH, Yamada, K, Nabeshima, T & Kim, HC 2009, 'Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence in mice', Journal of Neuroscience Research, vol. 87, no. 16, pp. 3679-3686. https://doi.org/10.1002/jnr.22166

Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence in mice. / Shin, Eun Joo; Bing, Guoying; Chae, Jong Seok; Kim, Tae Woo; Bach, Jae Hyung; Park, Dae Hun; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung Chun.

In: Journal of Neuroscience Research, Vol. 87, No. 16, 01.12.2009, p. 3679-3686.

Research output: Contribution to journalArticle

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AU - Shin, Eun Joo

AU - Bing, Guoying

AU - Chae, Jong Seok

AU - Kim, Tae Woo

AU - Bach, Jae Hyung

AU - Park, Dae Hun

AU - Yamada, Kiyofumi

AU - Nabeshima, Toshitaka

AU - Kim, Hyoung Chun

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