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Sleep-wake cycle disturbances and NeuN-altered expression in adult rats after cannabidiol treatments during adolescence.
Psychopharmacology (Berl). 2021 Jun; 238(6):1437-1447.P

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.

Authors+Show Affiliations

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. eric.murillo@anahuac.mx. Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico. eric.murillo@anahuac.mx.Depto. de Neurociencia Cognitiva, División de Neurociencias Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.Cognitive and Clinical Psychology Laboratory, Department of Human Sciences, European University of Rome, Rome, Italy.Cognitive and Clinical Psychology Laboratory, Department of Human Sciences, European University of Rome, Rome, Italy.Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico.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.Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico. Cognitive and Clinical Psychology Laboratory, Department of Human Sciences, European University of Rome, Rome, Italy.Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico. Laboratory of Physical Activity Neuroscience, Physical Activity Sciences Postgraduate Program, Salgado de Oliveira University, Niterói, Brazil. Laboratory of Physical Activity Neuroscience, Neurodiversity Institute, Queimados, Rio de Janeiro, Brazil.Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico. Faculty of Human Sciences, Medical School Hamburg, Hamburg, Germany.Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico. Laboratorio de Neurobiología del Sueño, Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33635384

Citation

Murillo-Rodríguez, Eric, et al. "Sleep-wake Cycle Disturbances and NeuN-altered Expression in Adult Rats After Cannabidiol Treatments During Adolescence." Psychopharmacology, vol. 238, no. 6, 2021, pp. 1437-1447.
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 (Berl). 2021;238(6):1437-1447.
Murillo-Rodríguez, E., Millán-Aldaco, D., Cicconcelli, D., Giorgetti, V., Arankowsky-Sandoval, G., Alcaraz-Silva, J., Imperatori, C., Machado, S., Budde, H., & Torterolo, P. (2021). Sleep-wake cycle disturbances and NeuN-altered expression in adult rats after cannabidiol treatments during adolescence. Psychopharmacology, 238(6), 1437-1447. https://doi.org/10.1007/s00213-021-05769-z
Murillo-Rodríguez E, et al. Sleep-wake Cycle Disturbances and NeuN-altered Expression in Adult Rats After Cannabidiol Treatments During Adolescence. Psychopharmacology (Berl). 2021;238(6):1437-1447. PubMed PMID: 33635384.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sleep-wake cycle disturbances and NeuN-altered expression in adult rats after cannabidiol treatments during adolescence. AU - Murillo-Rodríguez,Eric, AU - Millán-Aldaco,Diana, AU - Cicconcelli,Dorotea, AU - Giorgetti,Valentina, AU - Arankowsky-Sandoval,Gloria, AU - Alcaraz-Silva,Jocelyne, AU - Imperatori,Claudio, AU - Machado,Sérgio, AU - Budde,Henning, AU - Torterolo,Pablo, Y1 - 2021/02/26/ PY - 2020/09/18/received PY - 2021/01/20/accepted PY - 2021/2/27/pubmed PY - 2021/6/2/medline PY - 2021/2/26/entrez KW - Cannabinoids KW - Sleep KW - Suprachiasmatic nucleus KW - Δ9-Tetrahydrocannabinol SP - 1437 EP - 1447 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 238 IS - 6 N2 - 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/33635384/Sleep_wake_cycle_disturbances_and_NeuN_altered_expression_in_adult_rats_after_cannabidiol_treatments_during_adolescence_ L2 - https://dx.doi.org/10.1007/s00213-021-05769-z DB - PRIME DP - Unbound Medicine ER -