de St Hilaire-Kafi S, Gaillard J M
Service de la Recherche biologique et de Psychopharmacologie clinique, Institutions Universitaires de Psychiatrie, Chene-Bourg, Switzerland.
Neuropharmacology. 1988 Dec;27(12):1227-30. doi: 10.1016/0028-3908(88)90024-x.
This study examined whether pharmacological manipulation of serotonergic (5-HT) systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or combined with parachlorophenylalanine (pCPA), an inhibitor of the synthesis of 5-HT, 8-OH-DPAT, a 5-HT1A receptor agonist and fluvoxamine, an inhibitor of the reuptake of 5-HT. Flunitrazepam increased the amount of orthodox sleep, the latency of rapid eye movement (REM) sleep and decreased the amount of REM sleep. The drug pCPA decreased the total sleep time and the amount of orthodox and REM sleep. Administration of flunitrazepam to pCPA-pretreated rats induced orthodox sleep in an identical way to that found in the controls. The drug 8-OH-DPAT increased wakefulness and the latency of REM sleep. The association of flunitrazepam with 8-OH-DPAT abolished the increase in waking seen after 8-OH-DPAT alone. In contrast, the combined treatment with flunitrazepam and 8-OH-DPAT resulted in a lengthening of the latency of REM sleep significantly greater than that observed with the same dose of each drug alone. Fluvoxamine increased the latency a decrease the amount of REM sleep. The association of fluvoxamine with flunitrazepam induced a decrease in REM sleep, equal to the sum of the effects of the two drugs alone. Fluvoxamine did not modify the other effects of flunitrazepam. The present experiments demonstrate that the association of pCPA, 8-OH-DPAT and fluvoxamine, did not alter the hypnogenic effect of flunitrazepam. The possibility of an involvement of 5-HT mechanisms in the effect of flunitrazepam on the phasic events in sleep is questionable.
本研究检测了对血清素能（5-羟色胺，5-HT）系统进行药物调控是否会影响大鼠体内氟硝西泮的催眠作用。强效催眠药氟硝西泮单独使用，或与5-HT合成抑制剂对氯苯丙氨酸（pCPA）、5-HT1A受体激动剂8-羟基二丙胺基四氢萘（8-OH-DPAT）以及5-HT再摄取抑制剂氟伏沙明联合使用。氟硝西泮增加了正常睡眠量、快速眼动（REM）睡眠潜伏期，并减少了REM睡眠量。药物pCPA减少了总睡眠时间以及正常睡眠和REM睡眠量。给经pCPA预处理的大鼠施用氟硝西泮，诱导出正常睡眠，其方式与对照组相同。药物8-OH-DPAT增加了清醒时间和REM睡眠潜伏期。氟硝西泮与8-OH-DPAT联用消除了单独使用8-OH-DPAT后出现的清醒增加现象。相反，氟硝西泮与8-OH-DPAT联合治疗导致REM睡眠潜伏期延长，显著大于单独使用相同剂量的每种药物时所观察到的延长程度。氟伏沙明增加了潜伏期，减少了REM睡眠量。氟伏沙明与氟硝西泮联用导致REM睡眠减少，等于两种药物单独作用的效果之和。氟伏沙明未改变氟硝西泮的其他作用。本实验表明，pCPA、8-OH-DPAT和氟伏沙明的联用并未改变氟硝西泮的催眠作用。5-HT机制参与氟硝西泮对睡眠阶段事件作用的可能性值得怀疑。
