Decreased spinal morphine/clonidine antinociceptive synergism in morphine-tolerant mice.
Decreased spinal morphine/clonidine antinociceptive synergism in morphine-tolerant mice.
复制标题
吗啡耐受小鼠中脊髓吗啡/可乐定镇痛协同作用降低。
DOI：
10.1016/0024-3205(94)00963-5
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发表时间：
1995
期刊：
影响因子：
6.1
通讯作者：
Roerig,SC
中科院分区：
文献类型：
--
作者：
Roerig,SC
使用甩尾试验在安慰剂和植入吗啡颗粒的小鼠中检查脊髓注射阿片类药物和 α2 激动剂可乐定之间的镇痛相互作用。在植入安慰剂颗粒的动物中，同时给予吗啡和可乐定产生了协同镇痛作用。在植入吗啡颗粒的小鼠中，协同作用降低为相加相互作用。可乐定与 mu 激动剂 Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO)、δ 激动剂 D-Pen2-D-Pen5-脑啡肽 (DPDPE) 和 kappa 激动剂 U50-488H 之间的相互作用在安慰剂动物中也具有协同作用。在吗啡丸治疗的小鼠中，DPDPE/可乐定相互作用降低为拮抗相互作用，DAMGO/可乐定保持协同作用，而U50-488H/可乐定相互作用降低为相加相互作用。这些结果支持以下观点：吗啡脊髓/脊髓上协同作用取决于脊髓阿片类药物和α2受体之间的相互作用，并且这种相互作用的减少是涉及吗啡耐受性发展的机制。此外，与μ阿片受体相比，δ和κ受体似乎更多地参与吗啡/可乐定减少的相互作用。
The antinociceptive interactions between spinally administered opioids and the alpha2agonist clonidine were examined in placebo and morphine pellet-implanted mice using the tail flick test. In placebo pellet-implanted animals, coadministered morphine and clonidine produced a synergistic antinociceptive effect. In mice implanted with morphine pellets, the synergism decreased to an additive interaction. The interactions between clonidine and the mu agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO), the delta agonist D-Pen2-D-Pen5-Enkephalin (DPDPE), and the kappa agonist U50-488H were also synergistic in placebo animals. In morphine pellet treated mice the DPDPE/clonidine interaction decreased to an antagonistic interaction, the DAMGO/clonidine remained synergistic and the U50-488H/clonidine interaction decreased to additive. These results support the proposal that the morphine spinal/supraspinal synergism depends upon the interaction between spinal opioid and alpha2receptors and a decrease in this interaction is a mechanism involved in development of tolerance to morphine. In addition, delta and kappa receptors appeared to be more involved in the morphine/clonidine decreased interaction than did mu opioid receptors.