PRIMATE MODEL FOR THE HYPNOTIC EFFECTS OF MELATONIN

衰老与睡眠障碍有关， 昼夜节律，包括血清褪黑激素浓度： 老年人的夜间血清褪黑激素水平通常基本上 低于年轻人。生理和药理剂量 褪黑激素，它可以提高循环中褪黑激素的浓度， 通常发生在其上方或上方， 急性日间疲劳和嗜睡，降低性能， 显著降低了年轻健康人和老年人入睡潜伏期 受试者和老年失眠症患者。 这些潜在的机制 影响尚不清楚。 为了了解褪黑激素对人体的作用机制， 睡眠和行为，这将是有帮助的动物模型， 就像人类一样，褪黑激素在夜间的生理增加 分泌与夜间睡眠相关，即，白天活动的动物 物种 我们建议使用Macaca Nemestrina进行试点研究， 在这种非人类灵长类动物中探索以下假设：1.口服 褪黑激素治疗减少运动活动，促进早睡 发作，并增加睡眠效率，作为评估活动。2. 行为和睡眠促进作用的幅度和持续时间 褪黑激素的剂量依赖性，和; 3.这个灵长类动物模型将允许 检测褪黑激素对睡眠影响的可能变化， 在延长的2个月治疗期间，使用最低限度的 激素的有效剂量。 如果这种动物模型能够被开发出来， 探索：1.神经生理学和生化机制， 褪黑激素促进睡眠和行为作用的基础; 2.的 褪黑激素个体间变异的生理基础 在人类中观察到的影响; 3。可能的因果 与年龄相关的睡眠模式恶化与 松果体分泌活动减少。 这些知识最终可能 导致发展一种基于实验的战略， 老年人的褪黑激素替代疗法

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.