Faculty of Science, School of Psychology, University of Sydney, Sydney, NSW, Australia.
Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
Sleep. 2023 Jul 11;46(7). doi: 10.1093/sleep/zsad112.
Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioral processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest, and promote sleep. At present, little research has comprehensively characterized the neuropsychopharmacology of oxytocin-induced effects on sleep-wake behavior and no reconciliation of these two competing hypotheses has been proposed.
This study explored the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg-1) and intranasal (i.n.; 0.06, 1, 3 mg·kg-1) routes. Caffeine (i.p. and i.n.; 10 mg·kg-1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pretreatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg-1) followed by oxytocin (i.p.; 1 mg·kg-1) were also conducted.
In both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Several i.p. oxytocin-induced sleep-wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep-wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects.
These findings help reconcile competing hypotheses of oxytocin-induced effects on sleep-wake behavior: i.p. oxytocin promotes quiet wakefulness-a state of restful environmental awareness compatible with both oxytocin's anxiolytic effects and its enhancement of processing complex stimuli.
外源性给予神经肽催产素对各种神经行为过程产生多种影响，包括睡眠和觉醒。由于催产素可以增强对社会和恐惧相关环境线索的注意力，它应该促进觉醒和清醒。然而，由于催产素可以减轻压力、降低活动并引起焦虑缓解，催产素也可能为休息和促进睡眠做好大脑准备。目前，很少有研究全面描述催产素对睡眠-觉醒行为的神经精神药理学作用，也没有提出这两种相互竞争的假设的调和。
本研究使用基于无线电遥测的多导睡眠描记术，在成年雄性和雌性 Wistar 大鼠中探索催产素对睡眠-觉醒结果的影响。催产素通过腹腔内（i.p.；0.1、0.3 和 1 mg·kg-1）和鼻内（i.n.；0.06、1、3 mg·kg-1）途径给药。咖啡因（i.p. 和 i.n.；10 mg·kg-1）作为促觉醒的阳性对照给药。为了确定作用机制，还进行了催产素受体（OXTR）拮抗剂 L-368,899（i.p.；5 mg·kg-1）预处理实验，然后给予催产素（i.p.；1 mg·kg-1）。
在雄性和雌性大鼠中，i.p. 催产素以抑制活跃觉醒为代价促进安静觉醒，抑制非快速眼动（NREM）和快速眼动（REM）睡眠。i.p. 催产素引起的一些睡眠-觉醒变化是通过 OXTR 结合介导的。相比之下，在任何测试剂量下，i.n. 催产素均未改变大多数睡眠-觉醒结果。i.p. 和 i.n. 咖啡因均表现出促觉醒作用。
这些发现有助于调和催产素对睡眠-觉醒行为影响的相互竞争假设：i.p. 催产素促进安静觉醒-一种与催产素的抗焦虑作用及其增强处理复杂刺激能力相兼容的环境意识的休息状态。
