el Kafi B, Cespuglio R, Leger L, Marinesco S, Jouvet M
Department of Experimental Medicine, INSERM-U 52 CNRS-URA 1195, Claude Bernard University, Lyon, France.
Brain Res. 1994 Feb 21;637(1-2):211-21. doi: 10.1016/0006-8993(94)91235-1.
Several peptides exhibiting hypnogenic properties when administered i.p., i.v. or i.c.v. are now known. No data, however, are available concerning their targets in the brain. In the present work we hypothesize that the nucleus raphe dorsalis (nRD) may be one such target since it contains 2 sleep permissive components that must be influenced for sleep to occur. One of these components is serotoninergic in nature and gates the occurrence of ponto-geniculo-occipital (PGO) waves. The other, of unknown nature, influences tonic sleep phenomena. For hypnogenic peptides, a putative mechanism permitting the triggering and maintenance of sleep might consist of influencing both the above components. In the present work, 3 hypnogenic substances, CLIP (corticotropin-Like intermediate lobe peptide), VIP (vasoactive intestinal polypeptide) and DSIP (delta sleep inducing peptide), were injected into the nRD in order to determine whether these compounds still induce sleep by local administration. To verify that such local injections do not spread outside the nRD, radiolabelled CLIP and VIP were also injected. Autoradiograms obtained with either labeled CLIP or VIP indicate that these compounds, injected in a 0.2 microliter volume, do not spread outside the nRD. The sleep data obtained confirm that CLIP, at a dose of 10 ng, induces an increase in duration of paradoxical sleep (PS); this effect is observed only for injection sites located in the dorsolateral part of the nRD, an area where CLIP immunoreactive (IR) fibers are present. VIP, at a dose of 100 ng, also increases PS duration, whereas at 10 ng, only slow wave sleep duration is increased. In this case, the positive injection sites are scattered throughout the entire nRD as are the VIP-IR fibers. With DSIP, no sleep effect was found whatever the dose used or the site injected; in the same manner, no DSIP-IR fibers have been located in this structure. These data suggest that the nRD is a target for the expression of the hypnogenic properties of CLIP and VIP, but not for DSIP. The nature of the possible mechanisms permitting such expression are discussed.
目前已知有几种肽经腹腔内、静脉内或脑室内给药时具有催眠特性。然而，关于它们在大脑中的靶点尚无相关数据。在本研究中，我们推测中缝背核（nRD）可能是这样一个靶点，因为它包含两个允许睡眠的成分，睡眠的发生必须对其产生影响。其中一个成分本质上是血清素能的，控制着脑桥-膝状体-枕叶（PGO）波的出现。另一个成分性质不明，影响着紧张性睡眠现象。对于催眠肽来说，一种可能触发和维持睡眠的机制可能包括影响上述两个成分。在本研究中，将3种催眠物质，促肾上腺皮质激素样中叶肽（CLIP）、血管活性肠肽（VIP）和δ睡眠诱导肽（DSIP）注入nRD，以确定这些化合物通过局部给药是否仍能诱导睡眠。为了验证这种局部注射不会扩散到nRD之外，还注射了放射性标记的CLIP和VIP。用标记的CLIP或VIP获得的放射自显影片表明，以0.2微升体积注射的这些化合物不会扩散到nRD之外。获得的睡眠数据证实，剂量为10纳克的CLIP会导致异相睡眠（PS）持续时间增加；仅在位于nRD背外侧部分（存在CLIP免疫反应性（IR）纤维的区域）的注射部位观察到这种效应。剂量为100纳克的VIP也会增加PS持续时间，而剂量为10纳克时，仅慢波睡眠持续时间增加。在这种情况下，阳性注射部位与VIP-IR纤维一样散布在整个nRD中。使用DSIP时，无论使用何种剂量或注射部位，均未发现睡眠效应；同样，在该结构中未发现DSIP-IR纤维。这些数据表明，nRD是CLIP和VIP催眠特性表达的靶点，但不是DSIP的靶点。讨论了允许这种表达的可能机制的性质。
