Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Eur J Pharmacol. 2013 Feb 28;702(1-3):149-57. doi: 10.1016/j.ejphar.2013.01.058. Epub 2013 Feb 8.
Serotonin (5-HT) released from descending fibers plays important roles in spinal functions such as locomotion and nociception. 5-HT2A and 5-HT3 receptors are suggested to contribute to spinal antinociception, although their activation also contributes to neuronal excitation. In the neonatal spinal cord, DL-p-chloroamphetamine (pCA), a 5-HT releaser, inhibited both A fiber-evoked monosynaptic reflex potential (MSR) and C fiber-evoked slow ventral root potential (sVRP). The pCA-mediated inhibition was reversed by ketanserin (a 5-HT2A receptor antagonist) and tropisetron (a 5-HT3 receptor antagonist). Bath-applied 5-HT also inhibited MSR and sVRP; in this case, the actions of 5-HT were antagonized by ketanserin, but not by tropisetron. The pCA-evoked inhibition of sVRP was reduced by bicuculline (a GABAA receptor antagonist) and strychnine (a glycine receptor antagonist). Furthermore, ketanserin inhibited the pCA-evoked release of gamma-aminobutyric acid (GABA) and glycine, while tropisetron inhibited the pCA-evoked release of 5-HT. These results suggest that 5-HT released by pCA activates 5-HT2A receptors, which in turn stimulates the release of GABA/glycine and thereby blocks the spinal nociceptive pathway. 5-HT3 receptors may be involved in the facilitation of 5-HT release via a positive feedback process.
血清素（5-HT）从下行纤维释放，在脊髓功能如运动和伤害感受中发挥重要作用。5-HT2A 和 5-HT3 受体被认为有助于脊髓抗伤害感受，尽管它们的激活也有助于神经元兴奋。在新生脊髓中，5-HT 释放剂 DL-p-氯苯丙胺（pCA）抑制 A 纤维诱发的单突触反射电位（MSR）和 C 纤维诱发的慢腹根电位（sVRP）。pCA 介导的抑制作用可被酮色林（5-HT2A 受体拮抗剂）和曲匹司特（5-HT3 受体拮抗剂）逆转。5-HT 也可抑制 MSR 和 sVRP；在这种情况下，5-HT 的作用可被酮色林拮抗，但不能被曲匹司特拮抗。pCA 诱导的 sVRP 抑制作用可被毒蕈碱（GABAA 受体拮抗剂）和士的宁（甘氨酸受体拮抗剂）减弱。此外，酮色林抑制 pCA 诱导的 GABA 和甘氨酸释放，而曲匹司特抑制 pCA 诱导的 5-HT 释放。这些结果表明，pCA 释放的 5-HT 激活 5-HT2A 受体，进而刺激 GABA/甘氨酸释放，从而阻断脊髓伤害感受途径。5-HT3 受体可能通过正反馈过程参与促进 5-HT 释放。
