Activation of supraspinal NMDA receptors by both D-serine alone or in combination with morphine leads to the potentiation of antinociception in tail-flick test of rats.
Activation of supraspinal NMDA receptors by both D-serine alone or in combination with morphine leads to the potentiation of antinociception in tail-flick test of rats.
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DOI：
10.1016/j.ejphar.2007.02.042
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发表时间：
2007-06
影响因子：
5
通讯作者：
M. Yoshikawa;Kenji Ito;Miho Maeda;K. Akahori;Shigeru Takahashi;X. Jin;M. Matsuda;Toshiyasu Suzuki;T. Oka;Hiroyuki Kobayashi;A. Hashimoto
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文献类型：
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作者：
M. Yoshikawa;Kenji Ito;Miho Maeda;K. Akahori;Shigeru Takahashi;X. Jin;M. Matsuda;Toshiyasu Suzuki;T. Oka;Hiroyuki Kobayashi;A. Hashimoto
虽然有各种信息N-甲基-D-天冬氨酸（NMDA）受体阿片类药物诱导的抗伤害性感受在脊髓水平的影响，鲜为人知的是在脊髓上的水平的影响。为了阐明NMDA受体在脊髓上水平吗啡诱导的抗伤害作用中的作用，我们研究了侧脑室（i. c. v.）使用甩尾试验，单独或与吗啡组合施用D-丝氨酸（NMDA受体的甘氨酸位点的选择性激动剂）。i. c. v.管理的D-丝氨酸，但不是L-丝氨酸，单独产生的甩尾反应的剂量依赖性镇痛。D-丝氨酸也剂量依赖性地增强由i. c. v.给药吗啡诱导的抗伤害性效应，同时给药产生了累加效应。L-701，324（一种NMDA受体甘氨酸位点的选择性拮抗剂）的i. c. v.给药可剂量依赖性地减弱D-丝氨酸单独或与吗啡联合产生的抗伤害作用。此外，D-丝氨酸诱导的抗伤害作用的增强被拮抗纳洛酮，一种非选择性阿片受体拮抗剂的i. c. v.管理。这些观察结果，以及D-丝氨酸是NMDA受体甘氨酸位点的内源性和选择性共激动剂的事实，强烈提示D-丝氨酸激活脊髓上NMDA受体导致甩尾实验中的抗伤害感受增强，内源性D-丝氨酸可调节μ-阿片受体介导的镇痛作用通过NMDA受体的甘氨酸位点在脊髓上水平。
Although there is a variety of information concerning the effects of the N-methyl-D-aspartate (NMDA) receptor on opioid-induced antinociception at the spinal level, little is known about the effects at the supraspinal level. To clarify the role of the NMDA receptor on the morphine-induced antinociception at the supraspinal level, we investigated the effects of the intracerebroventricular (i.c.v.) administration of D-serine, a selective agonist for the glycine site of the NMDA receptors, alone or in combination with morphine using the tail-flick test. The i.c.v. administration of D-serine, but not L-serine, alone produced a dose-dependent antinociception in the tail-flick response. D-Serine also dose-dependently potentiated the antinociceptive effect induced by the i.c.v. administration of morphine and the simultaneous administration produced an additive effect. The potentiation of the antinociception produced by both D-serine alone or in combination with morphine was dose-dependently attenuated by the i.c.v. administration of L-701,324, a selective antagonist for the glycine site of the NMDA receptors. In addition, the potentiation of the D-serine-induced antinociception was antagonized by the i.c.v. administration of naloxone, a nonselective opioid receptor antagonist. These observations, together with the fact that D-serine is an endogenous and selective co-agonist for the glycine site of the NMDA receptors, strongly suggested that the activation of the supraspinal NMDA receptors by D-serine leads to the potentiation of the antinociception in the tail-flick test and that endogenous D-serine could modulate the μ-opioid receptor mediated antinociception via the glycine site of the NMDA receptors at the supraspinal level.