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  1. C100 医学部/医学系研究科
  2. C100d 学位論文
  3. 博士論文(医保博・論医保博)

The role of organic cation transporter-3 in methamphetamine disposition and its behavioral reponse in rats

http://hdl.handle.net/2237/10110
http://hdl.handle.net/2237/10110
74bf388f-8408-43f5-a429-db2593aeaa19
名前 / ファイル ライセンス アクション
080227_nakayama_manuscript-1.pdf 080227_nakayama_manuscript-1.pdf (182.1 kB)
080227_nakayama_figure-1.pdf 080227_nakayama_figure-1.pdf (1.0 MB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2008-06-02
タイトル
タイトル The role of organic cation transporter-3 in methamphetamine disposition and its behavioral reponse in rats
言語 en
著者 中山, 寛尚

× 中山, 寛尚

WEKO 23530

ja 中山, 寛尚

Search repository
Nakayama, Hironao

× Nakayama, Hironao

WEKO 23531

en Nakayama, Hironao

Search repository
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
抄録
内容記述 Organic cation transporter-3 (OCT3) is expressed in several tissues including the brain. We have previously demonstrated that rats with behavioral sensitization to methamphetamine (METH) increased the brain penetration of METH with decreased expression of OCT3 in brain. Considering the earlier in vitro studies demonstrating that 1) OCT3 could transport dopamine (DA) and 2) the specific transport via OCT3 could be inhibited by METH, these results suggest that decreased OCT3 might decrease the efflux of METH and/or DA from brain, subsequently causing the development of behavioral sensitization. Thus, in the present study, behavioral task related to DA and pharmacokinetic experiment were performed using rats treated with antisense against OCT3 (OCT3-AS) since no specific ligands for OCT3 are still available. The continuous infusion of OCT3-AS into the third ventricle significantly decreased the expression of OCT3 in choroid plexus (CP) epithelial cells. Both METH-induced hyperlocomotion and METH-induced extracellular DA levels in nucleus accumbens and prefrontal cortex were significantly increased in OCT3-AS-treated rats. Moreover, the concentrations of METH were significantly increased in cerebrospinal fluid as well as extracellular areas at the nucleus accumbens in OCT3-AS-treated rats. These results suggested that decreased OCT3 elevated the concentration of METH and/or DA in brain, subsequently enhancing dopaminergic neuronal transmission and increasing METH-induced hyperlocomotion. In summary, OCT3 at the CP could regulate the effect of METH by controlling the levels of METH and/or DA in brain. Thus, these results suggest that OCT3 may be a new molecular target to treat METH-related disorders such as drug abuse and schizophrenia.
言語 en
内容記述タイプ Abstract
内容記述
内容記述 名古屋大学博士学位論文 学位の種類:博士(医療技術学) (課程) 学位授与年月日:平成20年3月25日
言語 ja
内容記述タイプ Other
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_db06
タイプ doctoral thesis
書誌情報
発行日 2008-03-25
学位名
言語 ja
学位名 博士(医療技術学)
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 13901
言語 ja
学位授与機関名 名古屋大学
言語 en
学位授与機関名 NAGOYA University
学位授与年度
学位授与年度 2007
学位授与年月日
学位授与年月日 2008-03-25
学位授与番号
学位授与番号 甲第7761号
フォーマット
application/pdf
フォーマット
application/pdf
著者版フラグ
値 publisher
URI
識別子 http://hdl.handle.net/2237/10110
識別子タイプ HDL
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