Laboratorio de Neurociencias Moleculares e Integrativas Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab Mérida, Km. 15.5 Carretera Mérida-Progreso, Int. Km. 2 Carretera a Chablekal, C.P. 97308, Mérida, Yucatán, Mexico.
Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico.
Psychopharmacology (Berl). 2021 Jun;238(6):1437-1447. doi: 10.1007/s00213-021-05769-z. Epub 2021 Feb 26.
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.
Here, we investigated the effects upon behavior and neural activity in adulthood after long-term administrations of CBD in juvenile rats.
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.
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.
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.
大麻二酚（CBD）是大麻的一种成分，其医学用途的快速发展加速了 CBD 类药物在法律和社会上的认可，但也引发了人们对儿童早期长期使用 CBD 是否会在成年后产生不良神经生物学影响的质疑，包括睡眠障碍。鉴于青春期阶段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暴露于 CBD 后的睡眠-觉醒周期。
在此，我们研究了在幼年大鼠长期给予 CBD 后，其在成年期的行为和神经活动的影响。
我们从出生后第 30 天（PND）开始，每天用 CBD（5 或 30mg/kg）预处理幼年大鼠，持续 2 周。治疗结束后，在 PND80 分析睡眠-觉醒周期和 NeuN 表达。
我们发现，给青春期（出生后第 30 天）大鼠腹腔内注射 CBD（5 或 30mg/kg）14 天，会增加成年大鼠光照期间的觉醒和快速眼动睡眠减少，而在光照关闭期间，觉醒减少，慢波睡眠增加。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表现出睡眠反弹期的中断。最后，我们确定了在青春期慢性给予 CBD 如何影响成年大鼠下丘脑视交叉上核（与睡眠相关的脑区）的 NeuN 表达。
我们的研究结果对于解释在青春期长期暴露于 CBD 的成年大鼠的结果具有重要意义，并为 CBD 如何影响发育阶段的睡眠-觉醒周期和神经元活动提供了新的见解。
