Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord
Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord
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DOI：
10.1038/sj.bjp.0706854
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发表时间：
2006-11-01
影响因子：
7.3
通讯作者：
Seyrek, M.
中科院分区：
文献类型：
--
作者：
Dogrul, A.;Seyrek, M.
背景和目的：脊髓内的血清素能系统在全身吗啡的镇痛作用中发挥着重要作用。目前，七组 5-HT 受体 (5-HT1-7) 已得到表征。最近发现的 5-HT7 受体亚型之一是 5-HT7 受体。我们旨在研究脊髓 5-HT7 受体在全身吗啡镇痛作用中的作用。实验方法：通过使用选择性 5-HT7 受体拮抗剂 SB-269970、选择性 5-HT1A 受体拮抗剂 WAY，将脊髓 5-HT7 受体在全身吗啡镇痛作用中的参与与 5-HT1A 和 5-HT2 受体进行比较100635，选择性5-HT2拮抗剂酮色林以及非选择性5-HT1,(2),(7)受体拮抗剂米角林。通过辐射热甩尾测试评估伤害感受。 主要结果：I.t.施用SB-269970（10μg）和米角林（20mg）完全阻断了皮下细胞。以时间依赖性方式给予吗啡诱导的（1、3、5和10mgkg(-1)）镇痛作用。此外，i.t. SB-269970（1、3、10和20 mg）和米角林（1、5、10和20 mg）的给药剂量依赖性地抑制最大剂量吗啡（10mg kg(-1)，s.c.）的镇痛作用。它。给予 WAY 100635 (20 mg) 或酮色林 (20 mg) 不会改变吗啡诱导的 (1, 3, 5 和 10mg kg(-1), s.c.) 镇痛作用。结论和意义：这些发现表明，脊髓 5-HT7 受体参与全身吗啡的镇痛作用，但不涉及 5-HT1A 或 5-HT2 受体。
Background and purpose: The serotonergic system within the spinal cord have been proposed to play an important role in the analgesic effects of systemic morphine. Currently, seven groups of 5-HT receptors (5-HT1-7) have been characterized. One of the most recently identified subtypes of 5 HT receptor is the 5-HT7 receptor. We aimed to examine the role of spinal 5-HT7 receptors in the antinociceptive effects of systemic morphine.Experimental approach: The involvement of spinal 5-HT7 receptor in systemic morphine antinociception was compared to that of the 5-HT1A and 5-HT2 receptors by using the selective 5-HT7 receptor antagonist, SB-269970, the selective 5-HT1A receptor antagonist, WAY 100635, the selective 5-HT2 antagonist ketanserin as well as the non-selective 5-HT1,(2),(7) receptor antagonist, metergoline. Nociception was evaluated by the radiant heat tail-flick test.Key results: I.t. administration of SB-269970 (10 mu g) and metergoline (20 mg) completely blocked the s.c. administered morphine-induced (1, 3, 5 and 10mgkg(-1)) antinociception in a time-dependent manner. Additionally, i.t. administration of SB-269970 (1, 3, 10 and 20 mg) and metergoline (1, 5, 10 and 20 mg) dose dependently inhibited the antinociceptive effects of a maximal dose of morphine (10mg kg(-1), s.c.). I.t. administration of WAY 100635 (20 mg) or ketanserine (20 mg) did not alter morphine-induced (1, 3, 5 and 10mg kg(-1), s.c.) antinociception.Conclusion and implications: These findings indicate that the involvement of spinal 5-HT7, but not of 5-HT1A or of 5-HT2 receptors in the antinociceptive effects of systemic morphine.