Effects And Mechanism Of Substance P And Serotonin On Sleep-Wakefulness Cycle Of Rats

The present study investigated the effects and mechanism of substance P (SP) and serotonin (5-HT) on sleep-wakefulness cycle of rats and the role of in the ventrolateral preoptic area (vLPO) on behavioral activities by using brain stereotaxic, nucleus spile, microinjection, lesion of nucleus, polysomnography (PSG), immunohistochemistry and behavioral test.1 The effects of injecting SP into lateral cerebral ventricle on percent of sleep-wakefulness in rats1.1 Microinjection of SP (100nmol) into lateral cerebral ventricle enhanced sleep and reduced wakefulness compared with control, while SP receptor antagonist(N-acetyl-L-tryptophan 3, 5~bis(trifluoromethyl)-benzyl ester, 100nmol)had reverse effect.1.2 Microinjection of kainic acid (a kind of neural excitotoxic agent, KA, 0.4 g) into vLPO reduced sleep and enhanced wakefulness compared with control, and SP central sleep-promoting effect disappeared when vLPO lesion by KA.1.3 The expression of Fos in the vLPO increased compared with control when microinjection of SP (100nmol) into lateral cerebral ventricle.2 The effects of SP in the vLPO on percent of sleep-wakefulness in rats2.1 Microinjection of SP (10nmol) into vLPO enhanced sleep, especially deep slow wave sleep, and reduced wakefulness compared with control, while SP receptor (NK-1) antagonist (N-acetyl-L-tryptophan3, 5-bis (trifluoromethyl) -benzyl ester, lOnmol)had reverse effect.2.2 Microinjection of U73122, a kind of phospholipase C (PLC) inhibitor, reduced sleep and inhanced wakefulness; and SP sleep-promoting effect didn't show when pre-treating with U73122 thirty minutes before.2.3 Microinjection of 3-mercaptopropionic acid (3-MP, a kind of glutamate decarboxylase inhibitor) into vLPO. On the day of microinjection, sleep only decreased a little. On the second day, sleep marked decreased and wakefulness marked increased. On the third and fourth day, sleep and wakefulness stages resumed to normal. SP sleep-promoting effect didn't show when pre-treating with 3-MP on the previous day.2.4 The expression of SP increased in vLPO in total sleep deprivation of 24 hours compared with control with immunocytochemistry.3 Effects of serotonin in the vLPO on percent of sleep-wakefulness cycle in rats3.1 There was no significant effect when microinjection of 5-hydroxytryptophan (5-HTP, 0.5 |ig, serotonin precursor) into vLPO on sleep-wakefulness cycle, but microinjection of 5-HTP (1 g) and fluoxetine (6 g) led to wakefuness increased and sleep decreased. Microinjection of non-selective serotonin receptor antagonist methysergide (MS) led to the opposited effect.3.2 The percent of sleep-wakfulness caused by 5-HTP or MS were significant assiociated with time.3.3 Compared with control, the behavior activities increased when vLPO lesion by KA using open-field test and elevated plus maze test, but there were no statistaical difference between lesion group and control.The present study indicated:1. Substance P is a central sleep-promoting substance and vLPO is a target of central SP acting on.2. Substance P has sleep-promoting effect in the vLPO of rats, especially deep slow wave sleep. The sleep-promoting effect of SP is mediated by GABAergic neurons in vLPO.3. Total sleep deprivation up-regulates the expression of SP.4. Serotonin has wakefulness-promoting effect in the vLPO of rats.5. Ventrolateral preoptic area could inhibit rat behavioral activities, but there were no statistaical difference.