Rationale

The medical uses of cannabidiol (CBD), a constituent of the Cannabis sativa, have accelerated the legal and social acceptance for CBD-based medications but has also given the momentum for questioning whether the long-term use of CBD during the early years of life may induce adverse neurobiological effects in adulthood, including sleep disturbances. Given the critical window for neuroplasticity and neuro-functional changes that occur during stages of adolescence, we hypothesized that CBD might influence the sleep-wake cycle in adult rats after their exposure to CBD during the adolescence.

Objectives

Here, we investigated the effects upon behavior and neural activity in adulthood after long-term administrations of CBD in juvenile rats.

Methods

We pre-treated juvenile rats with CBD (5 or 30 mg/Kg, daily) from post-natal day (PND) 30 and during 2 weeks. Following the treatments, the sleep-wake cycle and NeuN expression was analyzed at PND 80.

Results

We found that systemic injections of CBD (5 or 30 mg/Kg, i.p.) given to adolescent rats (post-natal day 30) for 14 days increased in adulthood the wakefulness and decreased rapid eye movement sleep during the lights-on period whereas across the lights-off period, wakefulness was diminished and slow wave sleep was enhanced. In addition, we found that adult animals that received CBD during the adolescence displayed disruptions in sleep rebound period after total sleep deprivation. Finally, we determined how the chronic administrations of CBD during the adolescence affected in the adulthood the NeuN expression in the suprachiasmatic nucleus, a sleep-related brain region.

Conclusions

Our findings are relevant for interpreting results of adult rats that were chronically exposed to CBD during the adolescence and provide new insights into how CBD may impact the sleep-wake cycle and neuronal activity during developmental stages.

中文翻译：

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青春期大麻素处理后成年大鼠的睡眠觉醒周期障碍和NeuN改变的表达

基本原理

大麻的成分大麻素（CBD）的医学用途加速了基于CBD的药物的法律和社会认可，但也引发了人们质疑生命早期是否长期使用CBD的势头可能在成年期引起不良的神经生物学作用，包括睡眠障碍。考虑到青春期阶段发生的神经可塑性和神经功能变化的关键窗口，我们假设CBD可能会影响成年大鼠在青春期接触CBD后的睡眠觉醒周期。

目标

在这里，我们调查了长期服用CBD对幼年大鼠对成年行为和神经活动的影响。

方法

我们从出生后第30天（PND）到2周期间，对CBD（每天5或30 mg / Kg，每天）的未成年大鼠进行预处理。治疗后，以PND 80分析睡眠-觉醒周期和NeuN表达。

结果

我们发现，对青春期大鼠（出生后第30天）进行14天的全身性CBD注射（5或30 mg / Kg，腹腔注射），在成年期增加了清醒度，并减少了开灯期间眼睛快速运动的睡眠，而熄灯时间减少了清醒，增强了慢波睡眠。此外，我们发现在青春期接受CBD的成年动物在完全睡眠剥夺后，在睡眠反弹期间出现破坏。最终，我们确定了青春期CBD的长期给药如何在成年期影响视交叉上核（与睡眠有关的大脑区域）中的NeuN表达。

结论

我们的发现与解释在青春期长期暴露于CBD的成年大鼠的结果有关，并为CBD在发育阶段如何影响睡眠-觉醒周期和神经元活动提供了新见解。