PRIMATE MODEL FOR THE HYPNOTIC EFFECTS OF MELATONIN

衰老与睡眠障碍有关，与睡眠障碍有关 昼夜节律，包括血清褪黑素浓度： 老年人夜间血清褪黑素水平通常相当高 低于年轻人。生理剂量和药理剂量 褪黑素，将循环中的褪黑素浓度提高到 通常发生在夜间或远高于它的地方，被证明产生了 严重的白天疲劳和嗜睡，降低表现，并 显著缩短健康青年的入睡潜伏期 受试者和老年失眠症患者。这些问题背后的机制 影响尚不清楚。 为了了解褪黑素对人类的作用机制 睡眠和行为，这将是有帮助的动物模型 就像人类一样，夜间生理上褪黑激素的增加 分泌物与夜间睡眠相关，也就是说，在白天的动物中 物种。 我们建议利用猕猴进行一项初步研究，设计 在这种非人类的灵长类动物中，探索以下假设：1.口头 褪黑素治疗减少运动活动，促进早睡 起效，并提高睡眠效率，根据活动学评估。2. 行为和促进睡眠效果的大小和持续时间 褪黑素的含量是剂量依赖的，并且；3.这个灵长类动物模型将允许 检测褪黑素对睡眠和睡眠影响的可能变化 在延长的，2个月的治疗期内使用最低限度的行为 荷尔蒙的有效剂量。 如果能够开发出这样的动物模型，它将使我们能够进一步 探索：1.神经生理和生化机制 褪黑素促进睡眠和行为作用的基础； 褪黑素个体间变异的生理基础 已经在人类身上观察到的影响；以及；3.可能的原因 睡眠模式的增龄性恶化与健康的关系 松果体分泌活动的减少。这一知识最终可能 导致以实验为基础的战略的发展 老年人的褪黑素替代疗法。

Aging is associated with sleep disturbances, and with disruptions in circadian rhythms, including that in serum melatonin concentrations: nocturnal serum melatonin levels in the elderly are often substantially lower than in younger people. Physiologic and pharmacologic doses of melatonin, that raise circulating melatonin concentrations to level normally occurring nocturnally or well above it, were shown to produce acute daytime fatigue and sleepiness, to diminish performance, and to significantly reduce latency to sleep onset both in young healthy subjects and in elderly insomniacs. The mechanisms underlying these effects are not known. In order to understand the mechanisms by which melatonin acts on human sleep and behavior, it would be helpful to have an animal model in which, as in humans, the physiological nocturnal increase in melatonin secretion correlates with nocturnal sleep, i.e., in a diurnal animal species. We propose to conduct a pilot study using Macaca Nemestrina, designed to explore, in this non-human primate, the hypotheses that: 1. Oral melatonin treatment decreases motor activity, promotes earlier sleep onset, and increases sleep efficiency, as assessed actigraphically. 2. The magnitude and the duration of behavioral and sleep-promoting effects of melatonin is dose dependent, and; 3. This primate model will allow detection of possible changes in melatonin's effect on sleep and behavior during a prolonged, 2 month, treatment period using a minimum effective dose of the hormone. If such an animal model can be developed it will allow us to further explore: 1. The neurophysiologic and biochemical mechanisms that underlie melatonin's sleep-promoting and behavioral effects; 2. The physiologic basis of the interindividual variability in melatonin's effects, that has been observed in humans, and; 3. The possible causal relationship between the age-related deterioration in sleep patterns and a decrease in pineal secretory activity. This knowledge may ultimately lead to the development of an experimentally-based strategy for melatonin-replacement therapy in elderly humans.