Jouvet M
Rev Neurol (Paris). 1984;140(6-7):389-400.
The concept of hypnogenic factor(s) which could increase during sleep deprivation was initiated by Piéron in 1913. However this idea was not accepted. It is difficult indeed to differentiate a true sleep inducing factor from the numerous exogeneous or endogeneous factors which may facilitate sleep onset, slow wave sleep (SWS) and/or paradoxical sleep (PS). At the present time there is no true sleep inducing factor for which it has been proven that its inactivation would led to long lasting selective insomnia. A review of the effect of central peptides upon the sleep waking cycle of rats does not permit to isolate any true "sleep" peptide. Only vaso-intestinal peptide (VIP) has some true hypnogenic effect since its injection is able to restore sleep in insomniac PCPA pretreated rats. The serotonergic system of the raphe was considered first as a true hypnogenic system since its inactivation by lesion or inhibition of 5HT biosynthesis with PCPA led to a total insomnia which could be reversed into physiological sleep by a secondary injection of 5HTP (the direct precursor of 5HT). This hypothesis has been rejected recently. Indeed, it has been shown that the activity of 5HT neurons was higher during waking than during sleep. Moreover the release of 5HT and 5HIAA (as measured with voltametric method) is also higher during waking. The following hypothesis may solve these contradictions: when 5HT neurons are active during waking, they initiate through neurohormonal mechanisms the biosynthesis of sleep factor(s) which are stored until they trigger sleep. Thus the amount of waking may be correlated with subsequent sleep. Recent experiments favor the hypothesis of the 5HT directed biosynthesis of PS factor which may trigger PS even in PCPA pretreated cats which are depleted of 5HT. On the one hand, PCPA injection during PS instrumental deprivation is followed by a subsequent PS rebound despite 5HT depletion. On the other hand, transfer of CSF from a normal sleep deprived donor cat induces PS in a PCPA pretreated insomniac recipient cat.
1913年，皮埃龙提出了睡眠剥夺期间可能增加的催眠因子的概念。然而，这一观点并未被接受。要从众多可能促进入睡、慢波睡眠（SWS）和/或异相睡眠（PS）的外源性或内源性因素中区分出真正的睡眠诱导因子确实很困难。目前，还没有一种真正的睡眠诱导因子被证明其失活会导致长期的选择性失眠。对中枢肽对大鼠睡眠-觉醒周期的影响进行综述后，无法分离出任何真正的“睡眠”肽。只有血管活性肠肽（VIP）具有一些真正的催眠作用，因为注射它能够使经对氯苯丙氨酸（PCPA）预处理的失眠大鼠恢复睡眠。中缝核的血清素能系统最初被认为是一个真正的催眠系统，因为通过损伤或用PCPA抑制5-羟色胺（5HT）生物合成使其失活会导致完全失眠，而二次注射5-羟色氨酸（5HTP，5HT的直接前体）可将其逆转至生理睡眠。这一假设最近已被否定。事实上，已表明5HT神经元在清醒时的活性高于睡眠时。此外，清醒时5HT和5-羟吲哚乙酸（5HIAA，用伏安法测量）的释放也更高。以下假设可能解决这些矛盾：当5HT神经元在清醒时活跃时，它们通过神经激素机制启动睡眠因子的生物合成，这些因子被储存起来，直到触发睡眠。因此，清醒的时长可能与随后的睡眠相关。最近的实验支持5HT指导PS因子生物合成的假设，该因子即使在5HT耗竭的PCPA预处理猫中也可能触发PS。一方面，在PS工具性剥夺期间注射PCPA后，尽管5HT耗竭，但随后会出现PS反跳。另一方面，将来自正常睡眠剥夺供体猫的脑脊液转移到经PCPA预处理的失眠受体猫中会诱导PS。
