Differential effects of LY235959, a competitive antagonist of the NMDA receptor on kappa-opioid receptor agonist induced responses in mice and rats.
Differential effects of LY235959, a competitive antagonist of the NMDA receptor on kappa-opioid receptor agonist induced responses in mice and rats.
复制标题
LY235959（NMDA 受体的竞争性拮抗剂）对 kappa-阿片受体激动剂诱导的小鼠和大鼠反应的不同影响。
DOI：
10.1016/s0006-8993(96)01270-x
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发表时间：
1997
期刊：
影响因子：
2.9
通讯作者：
Thorat,SN
中科院分区：
文献类型：
--
作者：
Bhargava,HN;Thorat,SN
本文研究了N-甲基-d-天冬氨酸受体竞争性拮抗剂LY235959对κ阿片受体激动剂U-50,488H的镇痛、降温作用以及对这些作用的耐受性的影响。在小鼠中，在U-50,488H前10分钟单次注射LY235959并不改变后者的镇痛作用。同样，LY235959每天两次，连续4天慢性给药不能改变U-50,488H对小鼠的镇痛作用。反复给予LY235959可剂量依赖性地减弱小鼠对U-50,488H镇痛作用的耐受性。LY235959对大鼠有明显的镇痛作用，预先给予LY235959可增强U-50,488H的镇痛作用。降温作用也有类似的效果。LY235959可减轻大鼠对U-50,488H的耐受性，但不影响其降温作用。这些结果提供了证据，LY235959单独和与U-50,488H一起急性给药时，对小鼠和大鼠的伤害性反应和体温反应有不同的作用。然而，当动物被LY235959预处理时，在两种动物对U-50,488H镇痛作用的耐受性的发展中观察到相似的抑制作用。这些研究表明，κ受体参与了阿片类药物耐受的形成，并表明阿片类药物与阿片受体相互作用的生化后果并不是阿片类止痛药急性和慢性作用的唯一因素。
The effects of the competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, LY235959, were determined on the analgesic and hypothermic effects as well as on the development of tolerance to these effects of U-50,488H, a κ-opioid receptor agonist in mice and rats. In the mouse, a single injection of LY235959 given 10 min prior to U-50,488H did not modify the analgesic action of the latter. Similarly, chronic administration of LY235959 twice a day for 4 days did not modify U-50,488H-induced analgesia in mice. Repeated pretreatment of mice with LY235959 dose-dependently attenuated the development of tolerance to the analgesic actions of U-50,488H. In the rat, LY235959 by itself produced a significant analgesia and prior treatment of rats with LY235959 enhanced the analgesic action of U-50,488H. Similar effects were seen with the hypothermic action. Pretreatment of rats with LY235959 attenuated the development of tolerance to the analgesic but not to the hypothermic action of U-50,488H. These results provide evidence that LY235959 produces differential actions on nociception and thermic responses by itself and when given acutely with U-50,488H in mice and rats. However, when the animals are pretreated with LY235959, similar inhibitory effects are observed on the development of tolerance to the analgesic action of U-50,488H in both the species. These studies demonstrate an involvement of the NMDA receptor in the development of κ-opioid tolerance and suggest that the biochemical consequences of an opioid's interaction with the opioid receptor are not the only factors that contribute to the acute and chronic actions of opioid analgesic drugs.