Dorsal raphe nuclear stimulation of SCN serotonin release and circadian phase-resetting
Dorsal raphe nuclear stimulation of SCN serotonin release and circadian phase-resetting
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DOI：
10.1016/s0006-8993(00)01963-6
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发表时间：
2000-03-24
期刊：
影响因子：
2.9
通讯作者：
Ehlen, JC
中科院分区：
文献类型：
--
作者：
Glass, JD;DiNardo, LA;Ehlen, JC
5-羟色胺（5-HT）与哺乳动物昼夜节律的调节密切相关。然而，位于视交叉上核（SCN）的昼夜节律钟与其能神经支配的来源中脑中缝核之间的功能关系知之甚少。在以前的研究中，我们报道了电刺激中缝背核或中缝正中核（分别为DRN和MRN）诱导SCN中5-HT的释放。值得注意的是，DRN-而不是MRN-刺激的5-HT释放被5-HT 1，2，7拮抗剂metergoline阻断，表明DRN通过激活5-HT反应性多突触通路间接向SCN发出信号。在本研究中，预处理与5-HT 2，7拮抗剂，ritanserin，也显着抑制DRN电刺激SCN 5-HT的释放。然而，5-HT_（1A）拮抗剂NAN-190或5-HT_（2）拮抗剂酮色林和肉桂色林预处理对DRN刺激的5-HT释放几乎没有抑制作用。在补充的行为试验中，电刺激DRN在主观中午造成了1.3小时的提前自由运行的昼夜活动节律下恒定的黑暗，这是由metergoline抑制。总的来说，这些结果证明：（1）DRN刺激的SCN中的5-HT释放需要具有5-HT 7药理学特征的受体的中间靶标的激活;（2）DRN的电刺激诱导昼夜活动节律的相位重置;和（3）5-HT受体的激活对于该DRN刺激的昼夜相位重置是必需的。鉴于DRN神经元活动的动态变化与日常睡眠-活动周期有关，以及其与SCN和膝状体间小叶的功能联系，DRN可以用于向包括大脑昼夜节律系统的各个部位提供行为/唤醒状态信息。(C)2000由Elsevier Science B. V.出版，保留所有权利。
Serotonin (5-HT) is strongly implicated in the regulation of mammalian circadian rhythms. However, little is known of the functional relationship between the circadian clock located in the suprachiasmatic nucleus (SCN) and its source of serotonergic innervation, the midbrain raphe nuclei. In previous studies, we reported that electrical stimulation of the dorsal or median raphe nuclei (DRN and MRN, respectively) induced 5-HT release in the SCN. Notably, DRN- but not MRN-stimulated 5-HT release was blocked by the 5-HT1,2,7 antagonist, metergoline, suggesting that the DRN signals to the SCN indirectly via the activation of a 5-HT-responsive multisynaptic pathway. In the present study, pretreatment with the 5-HT2,7 antagonist, ritanserin, also significantly inhibited DRN-electrically stimulated SCN 5-HT release. However, pretreatment with the 5-HT1A antagonist, NAN-190, or the 5-HT2 antagonists ketanserin and cinanserin had Little suppressive effect on this DRN-stimulated 5-HT release. In complementary behavioral trials, electrical stimulation of the DRN during subjective midday caused a 1.3-h advance in the free-running circadian activity rhythm under constant darkness, which was inhibited by metergoline. Collectively, these results are evidence that: (1) DRN-stimulated 5-HT release in the SCN requires the activation of an intermediate target with receptors having 5-HT7 pharmacological characteristics; (2) electrical stimulation of the DRN induces phase-resetting of the circadian activity rhythm; and (3) activation of 5-HT receptors is necessary for this DRN-stimulated circadian phase-resetting. In view of the dynamic changes in DRN neuronal activity incumbent with the daily sleep-activity cycle, and its functional linkages to the SCN and intergeniculate leaflet, the DRN could serve to provide behavioral/arousal state information to various sites comprising the brain circadian system. (C) 2000 Published by Elsevier Science B.V. All rights reserved.