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SLEEP REGULATION INVOLVEMENT OF CHOLECYSTOKININ

缩胆囊素参与的睡眠调节

基本信息

批准号：
2703003
负责人：
LEVENTE KAPAS
金额：
$ 10.81万
依托单位：
FORDHAM UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-05-01 至 1999-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2703003
关键词：
blood chemistry body temperature regulation cholecystokinin circadian rhythms eating electroencephalography laboratory rat sex behavior sleep sleep regulatory center vagus nerve vasoactive intestinal peptide wakefulness

项目摘要

The broad objective of this proposal is to study the role of cholecystokinin (CCK) in the regulation of sleep-wake activity. Two distinct CCK pools are present in the body. CCK is a gastrointestinal peptide released from the small intestines, and also a neurotransmitter/neuromodulator in the nervous system. We hypothesize that peripheral CCK, present in the systemic circulation, contributes to the maintenance of normal sleep, and also mediates sleep responses to common daily activities which lead to sleep: eating and mating. Major evidence in support of this hypothesis includes: a) Systemic administration of CCK induces sleep in all species studied; results are from several independent laboratories, b) Systemic CCK, acting on peripheral structures, is capable of modulating complex higher nervous functions such as learning and hypothalamic hormone secretion, c) The two major stimuli for CCK production, eating and sexual activity, both induce characteristic sleep responses parallel to increased plasma CCK levels, and d) Released CCK, provides a feedback signal to feeding and sexual activity eliciting a typical behavioral syndrome, satiety. To test our hypothesis we propose to: l) test the effects of receptor specific CCK agonists and antagonists on spontaneous sleep; 2) correlate plasma CCK responses with sleep responses after eating and sexual activity; we will also test the effects of CCK receptor antagonists on those sleep responses accompanied with sexual- and feeding-satiety; and 3) we will determine the role of two possible peripheral mediators of sleep responses, the vagal nerve and vasoactive intestinal polypeptide, in CCK-induced sleep. The experiments will be carried out in rats chronically implanted with EEG electrodes, brain thermistors, and intracardial catheters. The proposed experiments will establish the role of CCK in physiological sleep. Almost everybody experiences sleep disturbance in his/her life time. However even today, when we are well into the decade of the brain, the treatments for disturbed sleep are exclusively on empirical bases. We have been able to manipulate vigilance for millennia, but we are still not able to restore physiological sleep. Unfortunately, we will not be able to do so until the physiological sleep signals/mechanisms are better understood.

这项建议的主要目标是研究胆囊收缩素（CCK）在睡眠-觉醒活动的调节。两不同的CCK池存在于体内。CCK是胃肠从小肠中释放的肽，神经系统中的神经递质/神经调质。我们假设存在于体循环中的外周CCK有助于维持正常的睡眠，也介导睡眠反应，导致睡眠的日常活动：进食和交配。主要证据在支持这一假设的包括：a）CCK的全身给药诱导睡眠在所有物种的研究;结果是从几个独立的实验室，B）作用于外周结构的全身性CCK能够调节复杂的高级神经功能，如学习和下丘脑激素分泌，c）CCK的两个主要刺激物生产、进食和性活动都能诱发特征性睡眠与增加的血浆CCK水平平行的反应，和d）释放的CCK，提供了一个反馈信号，以喂养和性活动引发一个典型的行为综合征饱腹感为了验证我们的假设， l）测试受体特异性CCK激动剂和拮抗剂的作用， 2）血浆CCK反应与睡眠相关饮食和性活动后的反应;我们还将测试影响 CCK受体拮抗剂对睡眠反应的影响性和喂养饱腹感; 3）我们将确定两个角色可能的睡眠反应的外周介质，迷走神经和血管活性肠多肽，在CCK诱导的睡眠。实验将在长期植入EEG电极的大鼠中进行，脑起搏器和心内导管。拟议的实验将建立CCK在生理睡眠中的作用。几乎每个人在他/她的一生中经历睡眠障碍。但即使在今天，当我们进入大脑的十年时，睡眠紊乱完全是基于经验的。我们已经能够几千年来，我们一直在操纵警惕，但我们仍然无法恢复生理睡眠不幸的是，我们将无法这样做，直到更好地理解生理睡眠信号/机制。