TY - JOUR
T1 - Sleep and neurochemical modulation by cannabidiolic acid methyl ester in rats
AU - Murillo-Rodríguez, Eric
AU - Arankowsky-Sandoval, Gloria
AU - Pertwee, Roger G.
AU - Parker, Linda
AU - Mechoulam, Raphael
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - Adenosine
KW - Cannabinoids
KW - Dopamine
KW - Sleep
KW - Wakefulness
UR - http://www.scopus.com/inward/record.url?scp=85076546426&partnerID=8YFLogxK
U2 - 10.1016/j.brainresbull.2019.12.006
DO - 10.1016/j.brainresbull.2019.12.006
M3 - Artículo
C2 - 31838151
AN - SCOPUS:85076546426
SN - 0361-9230
VL - 155
SP - 166
EP - 173
JO - Brain Research Bulletin
JF - Brain Research Bulletin
ER -