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Brain Res Bull. 2020 Feb;155:166-173. doi: 10.1016/j.brainresbull.2019.12.006. Epub 2019 Dec 12.

Sleep and neurochemical modulation by cannabidiolic acid methyl ester in rats.

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Laboratorio de Neurociencias Moleculares e Integrativas Escuela de Medicina, División Ciencias de la Salud Universidad Anáhuac Mayab Mérida, Yucatán, Mexico; Intercontinental Neuroscience Research Group, Mexico. Electronic address:
Centro De Investigaciones Regionales "Dr. Hideyo Noguchi" Universidad Autónoma de Yucatán. Mérida, Yucatán, Mexico.
School of Medicine School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Department of Psychology and Neuroscience Graduate Program University of Guelph, Guelph, Ontario, Canada.
Institute for Drug Research, Medical Faculty Hebrew University, Jerusalem, Israel.


Cannabidiolic acid methyl ester (HU-580) is a more stable compound than cannabidiolic acid (CBDA) which has been shown to be effective in reducing nausea, anxiety, depression behaviors in animal models. Here we extend the investigation of this compound to determine its effect on the sleep-wake cycle in male Wistar rats. HU-580 dose-dependently (0.1, 1.0 or 100 μg/Kg, i.p.) prolonged wakefulness (W) and decreased slow wave sleep (SWS) duration whereas rapid eye movement sleep (REMS) showed no statistical change. In addition, the brain microdialysis probes either placed at nucleus accumbens (NAc) or into the basal forebrain in freely moving animals were used to evaluate the effects of HU-580 treatment on neurotransmitters related to the sleep-wake cycle modulation. HU-580 enhanced extracellular levels of dopamine, serotonin collected from NAc while adenosine and acetylcholine were increased in basal forebrain. In summary, HU-580 seems to possess wake-promoting pharmacological properties and enhances the levels of wake-related neurochemicals. This is the first report of effects of HU-580 on sleep modulation expanding the very limited existent data on the neurobiological effects of HU-580 on rats.


Adenosine; Cannabinoids; Dopamine; Sleep; Wakefulness

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