Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.

<h4>Background</h4>The N-methyl-D-aspartate (NMDA) receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine (METH). Serine racemase (SRR) is an enzyme which synthesizes D-serine, an endogenous co-agonist of NMDA receptors. Us...

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Autores principales:	Mao Horio, Mami Kohno, Yuko Fujita, Tamaki Ishima, Ran Inoue, Hisashi Mori, Kenji Hashimoto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9307bc56b24547a3a3eb1b32800dff58
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spelling	oai:doaj.org-article:9307bc56b24547a3a3eb1b32800dff582021-11-18T07:21:44ZRole of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.1932-620310.1371/journal.pone.0035494https://doaj.org/article/9307bc56b24547a3a3eb1b32800dff582012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22530033/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The N-methyl-D-aspartate (NMDA) receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine (METH). Serine racemase (SRR) is an enzyme which synthesizes D-serine, an endogenous co-agonist of NMDA receptors. Using Srr knock-out (KO) mice, we investigated the role of SRR on METH-induced behavioral abnormalities in mice.<h4>Methodology/principal findings</h4>Evaluations of behavior in acute hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP) were performed. The role of SRR on the release of dopamine (DA) in the nucleus accumbens after administration of METH was examined using in vivo microdialysis technique. Additionally, phosphorylation levels of ERK1/2 proteins in the striatum, frontal cortex and hippocampus were examined using Western blot analysis. Acute hyperlocomotion after a single administration of METH (3 mg/kg) was comparable between wild-type (WT) and Srr-KO mice. However, repeated administration of METH (3 mg/kg/day, once daily for 5 days) resulted in behavioral sensitization in WT, but not Srr-KO mice. Pretreatment with D-serine (900 mg/kg, 30 min prior to each METH treatment) did not affect the development of behavioral sensitization after repeated METH administration. In the CPP paradigm, METH-induced rewarding effects were demonstrable in both WT and Srr-KO mice. In vivo microdialysis study showed that METH (1 mg/kg)-induced DA release in the nucleus accumbens of Srr-KO mice previously treated with METH was significantly lower than that of the WT mice previously treated with METH. Interestingly, a single administration of METH (3 mg/kg) significantly increased the phosphorylation status of ERK1/2 in the striatum of WT, but not Srr-KO mice.<h4>Conclusions/significance</h4>These findings suggest first, that SRR plays a role in the development of behavioral sensitization in mice after repeated administration of METH, and second that phosphorylation of ERK1/2 by METH may contribute to the development of this sensitization as seen in WT but not Srr-KO mice.Mao HorioMami KohnoYuko FujitaTamaki IshimaRan InoueHisashi MoriKenji HashimotoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35494 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mao Horio Mami Kohno Yuko Fujita Tamaki Ishima Ran Inoue Hisashi Mori Kenji Hashimoto Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
description	<h4>Background</h4>The N-methyl-D-aspartate (NMDA) receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine (METH). Serine racemase (SRR) is an enzyme which synthesizes D-serine, an endogenous co-agonist of NMDA receptors. Using Srr knock-out (KO) mice, we investigated the role of SRR on METH-induced behavioral abnormalities in mice.<h4>Methodology/principal findings</h4>Evaluations of behavior in acute hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP) were performed. The role of SRR on the release of dopamine (DA) in the nucleus accumbens after administration of METH was examined using in vivo microdialysis technique. Additionally, phosphorylation levels of ERK1/2 proteins in the striatum, frontal cortex and hippocampus were examined using Western blot analysis. Acute hyperlocomotion after a single administration of METH (3 mg/kg) was comparable between wild-type (WT) and Srr-KO mice. However, repeated administration of METH (3 mg/kg/day, once daily for 5 days) resulted in behavioral sensitization in WT, but not Srr-KO mice. Pretreatment with D-serine (900 mg/kg, 30 min prior to each METH treatment) did not affect the development of behavioral sensitization after repeated METH administration. In the CPP paradigm, METH-induced rewarding effects were demonstrable in both WT and Srr-KO mice. In vivo microdialysis study showed that METH (1 mg/kg)-induced DA release in the nucleus accumbens of Srr-KO mice previously treated with METH was significantly lower than that of the WT mice previously treated with METH. Interestingly, a single administration of METH (3 mg/kg) significantly increased the phosphorylation status of ERK1/2 in the striatum of WT, but not Srr-KO mice.<h4>Conclusions/significance</h4>These findings suggest first, that SRR plays a role in the development of behavioral sensitization in mice after repeated administration of METH, and second that phosphorylation of ERK1/2 by METH may contribute to the development of this sensitization as seen in WT but not Srr-KO mice.
format	article
author	Mao Horio Mami Kohno Yuko Fujita Tamaki Ishima Ran Inoue Hisashi Mori Kenji Hashimoto
author_facet	Mao Horio Mami Kohno Yuko Fujita Tamaki Ishima Ran Inoue Hisashi Mori Kenji Hashimoto
author_sort	Mao Horio
title	Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
title_short	Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
title_full	Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
title_fullStr	Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
title_full_unstemmed	Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
title_sort	role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9307bc56b24547a3a3eb1b32800dff58
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Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine.

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