Effects of κ-Agonist on the Antinociception and Locomotor Enhancing Action Induced by Morphine in Mice
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概要
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The antinociception of intracerebroventricular injection (i.c.v.) of morphine was markedly abolished by pretreatment with naloxonazine (μ<SUB>1</SUB>-antagonist), s.c.; β-funaltrexamine (μ<SUB>1</SUB>/μ<SUB>2</SUB>-antagonist), i.c.v.; DSP-4 (noradrenaline neurotoxin), s.c.; or <I>p</I>-chlorophenylalanine (serotonin synthesis inhibitor), s.c. in the mouse 55°C hot-plate assay. Pretreatment with nor-binaltorphimine (κ-antagonist), i.c.v. or PCPA, s.c. drastically blocked the κ-agonist U-50, 48811-induced supraspinal antinociception. These findings in dicate either noradrenergic or serotonergic involvement in the mediation of the antinociception of i.c.v.-morphine through μ-receptors. On the contrary, the antinociception of i.c.v. U-50, 488H through κ-receptors appears to depend on the serotonergic but not noradrenergic systems. The antinociceptive interaction between the i.c.v.-morphine and -U-50, 488H was an additive effect. On the other hand, i.c.v.-morphine dose-dependently increased the locomotion in mice, and this hyperlocomotion of morphine was drastically blocked by pretreatment with either β-funaltrexamine, i.c.v. or 6-hydroxydopamine (dopamine depletor), i.c.v. I.c.v.-U-50, 488H dose-dependently reduced the increasing locomotion of i.c.v.-morphine, but not that of s.c.-apomorphine (dopamine receptor agonist), and this effect of U-50, 488H was completely reversed by pretreatment with nor-binaltorphimine, i.c.v. These results suggest that coadministration of κ-agonists can suppress the dopamine-related hyperlocomotion of μ-agonists without decreasing the antinociception of μ-agonists in mice.
著者
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Misawa Miwa
Department Of Applied Pharmacology Hoshi University
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Narita Minoru
Department Of Anesthesiology Medical College Of Wisconsin
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Nagase Hiroshi
Basic Research Laboratories Toray Industries Inc.
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Suzuki Tsutomu
Department Of Applied And Environmental Chemistry Kitami Institute Of Technology
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Takahashi Yuki
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University
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Takahashi Yuki
Department of Pharmacology, School of Pharmacy, Hoshi University
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Takamori Kazuaki
Department of Pharmacology, School of Pharmacy, Hoshi University
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Funada Masahiko
Department of Pharmacology, School of Pharmacy, Hoshi University
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Narita Minoru
Department of Pharmacology, School of Pharmacy, Hoshi University
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