Zhang Gongliang, Wang Liecheng, Liu Huan, Zhang Jingxing
Sleep Research Laboratory, Anhui Medical University, Hefei, Anhui province 230022, P.R. China.
Brain Res. 2004 Dec 3;1028(2):225-32. doi: 10.1016/j.brainres.2004.09.017.
Substance P (SP) has been characterized as an excitatory neurotransmitter and/or neuromodulator in the peripheral and central nervous systems. It is involved in mediating various biological functions such as smooth muscle contraction, neuronal excitation, and pain transmission. Although Lieb et al. reported that intravenous infusion of SP into healthy men led to an increase of paradoxical sleep latency and time awake, little is known about the function and target of SP on sleep-wakefulness cycle in the central nervous system. The ventrolateral preoptic area (vLPO) plays an important role in modulation of sleep-wakefulness cycle. The present study investigated the effect of SP on sleep-wakefulness cycle in the vLPO of rats. Slow wave sleep (SWS) was enhanced after SP was microinjected into bilateral vLPO, while SP receptor antagonist, N-acetyl-l-tryptophan 3,5-bis(trifluoromethyl)-benzyl ester, led to the opposite effect. The effect induced by SP was blocked by U73122, a phospholipase C inhibitor. In addition, 3-mercaptopropionic acid, a glutamic acid decarboxylase inhibitor that inhibits gamma-aminobutyric acid (GABA) synthesis and release, blocked the SP-induced sleep-promoting effect in the vLPO. These results indicate that SP has sleep-promoting effect in the vLPO possibly by GABAergic neurons.
P物质（SP）已被确定为外周和中枢神经系统中的一种兴奋性神经递质和/或神经调质。它参与介导各种生物学功能，如平滑肌收缩、神经元兴奋和疼痛传递。尽管Lieb等人报告称，向健康男性静脉输注SP会导致异相睡眠潜伏期和清醒时间增加，但关于SP在中枢神经系统睡眠-觉醒周期中的功能和靶点知之甚少。腹外侧视前区（vLPO）在调节睡眠-觉醒周期中起重要作用。本研究调查了SP对大鼠vLPO中睡眠-觉醒周期的影响。将SP微量注射到双侧vLPO后，慢波睡眠（SWS）增强，而SP受体拮抗剂N-乙酰-L-色氨酸3,5-双（三氟甲基）苄酯则产生相反的效果。SP诱导的效应被磷脂酶C抑制剂U73122阻断。此外，抑制γ-氨基丁酸（GABA）合成和释放的谷氨酸脱羧酶抑制剂3-巯基丙酸阻断了vLPO中SP诱导的促睡眠效应。这些结果表明，SP可能通过GABA能神经元在vLPO中具有促睡眠作用。
