Abstract
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.
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Acknowledgements
The authors thank to the Staff of the Rat Vivarium from Escuela de Medicina, Universidad Anáhuac Mayab (Mérida, Yucatán, Mexico) for their assistance with the care and maintenance of laboratory rodents.
Funding
This work was supported by the University of California Institute for Mexico and the United States (UC MEXUS) and Consejo Nacional de Ciencia y Tecnología (CONACyT, Mexico) under Grant CN-17-19 and Escuela de Medicina, Universidad Anáhuac Mayab (Mérida, Yucatán, Mexico) under Grant PresInvEMR2018 given to E. M. R.
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Murillo-Rodríguez, E., Millán-Aldaco, D., Cicconcelli, D. et al. Sleep-wake cycle disturbances and NeuN-altered expression in adult rats after cannabidiol treatments during adolescence. Psychopharmacology 238, 1437–1447 (2021). https://doi.org/10.1007/s00213-021-05769-z
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DOI: https://doi.org/10.1007/s00213-021-05769-z