Methadone and Heroin Antinociception: Predominant δ-Opioid-Receptor Responses in Methadone-Tolerant Mice

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Antinociceptive tail flick responses to heroin and 6-monoacetylmorphine mediated in the brain by μ-opioid receptor are switched by morphine pellet implantation to δ<sub>1</sub>-and δ<sub>2</sub>-opioid-receptors mediation, respectively. Present results showed that the μ-receptor response (inhibited by β-funaltrexamine) to methadone was changed by morphine pellet implantation to δ<sub>1</sub> (inhibited by 7-benzylidenenaltrexone)- and δ<sub>2</sub> (inhibited by naltriben)-opioid-receptor responses. Methadone pellet implantation likewise changed mediation from μ- to δ-opioid receptors for heroin and methadone but not for morphine (β-funaltrexamine continued to inhibit). Methadone μ action in the brain was linked through a descending system to activate spinal serotonin receptors (inhibited by methysergide), but this link was gone in the methadone-pellet-implanted group. In the latter group, the new δ<sub>1</sub>- and δ<sub>2</sub>-receptor responses were mediated by spinal GABA<sub>A</sub> (inhibited by bicuculline) and GABA<sub>B</sub> (inhibited by 2-hydroxysaclofen) receptors. These shifts in neuronal systems meant that μ receptors on a given neuron were not changed into δ receptors. Preliminary results showed that δ-agonist action for methadone was prevented from appearing by MK801, a NMDA-receptor antagonist, and did not occur in 129S6/SvEv mice which lack NMDA responsiveness. Could methadone maintenance treatment in humans uncover δ-agonist actions?

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 88(3), 319-331, 2002-03-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008187965
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    6119592
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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