Substance P promotes sleep in the ventrolateral preoptic area of rats

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.