麻薬依存形成·禁断症状発現における脳内グリア型グルタミン酸トランスポーターの役割に関する検討

• 中川 貴之

  京都大学大学院薬学研究科

書誌事項

タイトル別名

• Involvement of Glial Glutamate Transporters in Morphine Dependence and Naloxone-Precipitated Withdrawal
• 麻薬依存形成・禁断症状発現における脳内グリア型グルタミン酸トランスポーターの役割に関する検討
• マヤク イゾン ケイセイ キンダン ショウジョウ ハツゲン ニ オケル ノウナイ グリアガタ グルタミンサン トランスポーター ノ ヤクワリ ニ カンスル ケントウ

抄録

A body of evidence supports that excitatory amino acid systems, particularly glutamatergic one, participate in morphine dependence and naloxone-precipitated withdrawal. In this study, we examined the involvement of glial glutamate transporters, GLT-1 and GLAST, in them. Rats were rendered morphine-depndent by subcutaneous implantation of two 75 mg morphine pellets for 5 days. Intracerebroventricular administration of DL-threo-β-benzyloxyaspartate, a glutamate transporter inhibitor significantly facilitated various naloxone-precipitated withdrawal signs. By northern blot analysis, the expression of GLT-1 mRNA was found to decrease significantly in the striatum and thalamus of morphine-dependent rats, and to increase significantly in the striatum 2 hr after the naloxone-precipitated withdrawal. On the other hand, there were no significant changes in GLAST mRNA levels in any brain regions. In vivo microdialysis experiments revealed that the extracellular glutamate levels was elevated in the striatum and nucleus accumbens, in which the changes of GLT-1 mRNA level were observed, during naloxone-precipitated morphine withdrawal. In cultured astrocytes, the expression of GLT-1 mRNA was regulated by agents activating the cAMP pathway, as well as β-adrenergic agonist and dopamine, but not morphine. These results suggest that the changes of GLT-1 expresson, which alter the glutamate uptake and affect the glutamatergic transmission efficiency, play a role in the development of morphine dependence and the expression of morphine withdrawal.

収録刊行物

• 薬学雑誌

  薬学雑誌 121 (9), 671-677, 2001-09-01

  公益社団法人 日本薬学会

キーワード

• morphine
• dependence
• glutamate transporter
• GLT-1
• GLAST
• withdrawal

詳細情報

• CRID: 1390001206126929536
• NII論文ID: 110003661160
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.121.671
• COI: 1:CAS:528:DC%2BD3MXms1eit7o%3D
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 5891603
• PubMed: 11558151
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5891603
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/121/9/121_9_671/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2002093007
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可