Sleep and neurochemical modulation by cannabidiolic acid methyl ester in rats
- ,
- Gloria Arankowsky-Sandovalb(Author),
- Roger G. Pertweee(Author),
- Linda Parkerd(Author),
- Raphael Mechoulamc(Author)
- ,
- bUniversidad Autonoma de Yucatan,
- cHebrew University of Jerusalem,
- dUniversity of Guelph,
- eUniversity of Aberdeen,
- fIntercontinental Neuroscience Research Group
Publication Information
Output type
Original language
EnglishPages from-to (Number of pages)
Pages 166-173 (8 pages)Journal (Volume, Issue Number)
Brain Research Bulletin (Volume 155)Publication milestones
- Published - 01/02/2020
Publication status
ISSN
0361-9230External Publication IDs
- Scopus: 85076546426
- PubMed: 31838151
Abstract
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.