Sakaguchi Minoru, Koseki Makoto, Wakamatsu Masanori, Matsumura Eiko
Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Eur J Pharmacol. 2006 Jan 13;530(1-2):81-7. doi: 10.1016/j.ejphar.2005.11.014. Epub 2005 Dec 15.
The effects of systemic administration of bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), a mu-opioid receptor agonist derived from milk beta-casein, on spontaneous alternation behavior in the Y-maze (spatial short-term memory) and step-down-type passive avoidance response (non-spatial long-term memory) were investigated in mice. Intraperitoneal (i.p.) administration of beta-casomorphin-5 (0.1-20 mg/kg) did not have a significant effect on either spontaneous alternation behavior or passive avoidance response. However, a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improved scopolamine (1 mg/kg, s.c.)-induced impairment of spontaneous alternation behavior and passive avoidance response. Pretreatment with intracerebroventricular injections of beta-funaltrexamine (a mu-opioid receptor antagonist, 0.1 microg/mouse) and naloxonazine (a mu(1)-opioid antagonist, 5 microg/mouse), which did not improve scopolamine-induced impairment, prevented the ameliorating effect of beta-casomorphin-5 on scopolamine-induced impairment of passive avoidance response. These results indicated that systemic administration of a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improves the disturbance of learning and memory resulting from cholinergic dysfunction through central mediation involving mu(1)-opioid receptors.
研究了源自牛奶β-酪蛋白的μ-阿片受体激动剂牛β-酪蛋白吗啡-5（酪酪五肽，Tyr-Pro-Phe-Pro-Gly）全身给药对小鼠Y迷宫中自发交替行为（空间短期记忆）和避暗式被动回避反应（非空间长期记忆）的影响。腹腔注射β-酪蛋白吗啡-5（0.1 - 20 mg/kg）对自发交替行为或被动回避反应均无显著影响。然而，低剂量（1 mg/kg，腹腔注射）的β-酪蛋白吗啡-5可改善东莨菪碱（1 mg/kg，皮下注射）诱导的自发交替行为和被动回避反应损伤。预先脑室内注射β-芬太尼环唑（一种μ-阿片受体拮抗剂，0.1 μg/小鼠）和纳洛酮嗪（一种μ(1)-阿片拮抗剂，5 μg/小鼠），这两种药物不能改善东莨菪碱诱导的损伤，却能阻止β-酪蛋白吗啡-5对东莨菪碱诱导的被动回避反应损伤的改善作用。这些结果表明，低剂量（1 mg/kg，腹腔注射）的β-酪蛋白吗啡-5全身给药通过涉及μ(1)-阿片受体的中枢介导作用改善了胆碱能功能障碍引起的学习和记忆障碍。
