SLEEP REGULATION INVOLVEMENT OF CHOLECYSTOKININ

这项建议的广泛目标是研究 CCK在睡眠-觉醒活动调节中的作用二 体内存在明显的CCK池。CCK是一种胃肠道 从小肠释放的肽，也是一种 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 维持正常睡眠，也调节睡眠对共同的反应 导致睡眠的日常活动：吃饭和交配。主要证据在 对这一假说的支持包括：a)CCK的系统给药 在所有被研究物种中诱导睡眠；结果来自几个独立的 实验室，b)作用于外周结构的系统性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 生产、进食和性行为都会导致特有的睡眠 与血浆CCK水平升高平行的反应，以及d)释放CCK， 为进食和性行为提供反馈信号，从而引发 典型的行为综合症，饱腹感。为了检验我们的假设，我们建议 L)测试受体特异性CCK激动剂和拮抗剂的作用 2)血浆CCK反应与睡眠的关系 进食和性行为后的反应；我们还将测试它们的影响 CCK受体拮抗剂对伴发睡眠反应的影响 性饱足感和喂食性饱足感；3)我们将确定两个角色 睡眠反应的可能外周介质，迷走神经和 血管活性肠肽，在CCK诱导的睡眠中。这些实验 将在长期植入脑电电极的大鼠身上进行， 脑部热敏电阻和心内导管。拟议中的实验 将确立CCK在生理睡眠中的作用。几乎每个人 在一生中经历过睡眠障碍。然而，即使在今天， 当我们进入大脑的十年时，治疗 受干扰的睡眠完全是基于经验。我们已经能够 操纵了几千年的警戒，但我们仍然无法恢复 生理睡眠。不幸的是，我们无法做到这一点，直到 生理睡眠信号/机制被更好地理解。

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.