Andersen Monica L, Nascimento Danielle C, Machado Ricardo B, Roizenblatt Suely, Moldofsky Harvey, Tufik Sergio
Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), Brazil.
Behav Brain Res. 2006 Feb 28;167(2):212-8. doi: 10.1016/j.bbr.2005.09.008. Epub 2005 Oct 11.
Substance P (SP) and neurokinins have been implicated in modulating pain and mood but little is known about their effect on sleep-wake behavior. The purpose of the present study was to examine the possible involvement of SP in sleep-wake mechanisms without activation of painful responses. Electrophysiological recordings of the sleep-wake cycle were conducted in C57BL/6J male mice that had intracerebral ventricular cannula inserted for drug administration. Initially, in order to determine the highest dose of SP that would not induce nociceptive response, 10 animals per group received administration of either SP doses or artificial cerebrospinal fluid (CSF-sham group) through the cannula and were assessed by the hot plate test. The sleep-wake cycle of two other groups of mice was recorded for 24 h before (baseline) and after receiving CSF (n=10) or SP-1 mM (n=11), dose that had been determined in the previous hot plate test. SP interfered with sleep, when compared to baseline and to sham group, by reducing sleep efficiency, increasing latency of sleep and the number of awakening bouts. To examine the reversal of SP effects, eight mice were administered with an NK1 receptor antagonist before SP administration. Prior administration of the NK1 antagonist prevented the disturbances in sleep.
The results suggest that SP produces disturbances in sleep, likely mediated by the NK1 receptor.
P物质（SP）和神经激肽与疼痛和情绪调节有关，但它们对睡眠-觉醒行为的影响知之甚少。本研究的目的是在不激活疼痛反应的情况下，研究SP在睡眠-觉醒机制中的可能作用。对插入脑室内插管用于给药的C57BL/6J雄性小鼠进行睡眠-觉醒周期的电生理记录。最初，为了确定不会诱发伤害性反应的SP最高剂量，每组10只动物通过插管接受SP剂量或人工脑脊液（假脑脊液组）给药，并通过热板试验进行评估。另外两组小鼠的睡眠-觉醒周期在接受脑脊液（n = 10）或1 mM SP（n = 11）之前（基线）和之后记录24小时，1 mM SP是在前一个热板试验中确定的剂量。与基线和假手术组相比，SP通过降低睡眠效率、增加睡眠潜伏期和觉醒次数来干扰睡眠。为了研究SP作用的逆转，八只小鼠在给予SP之前给予NK1受体拮抗剂。预先给予NK1拮抗剂可防止睡眠紊乱。
结果表明，SP会导致睡眠紊乱，可能是由NK1受体介导的。
