TY - JOUR
T1 - Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats
AU - Murillo-Rodríguez, Eric
AU - Millán-Aldaco, Diana
AU - Palomero-Rivero, Marcela
AU - Mechoulam, Raphael
AU - Drucker-Colín, René
PY - 2006/8/7
Y1 - 2006/8/7
N2 - Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Δ9-THC modulates sleep, but no clear evidence on the role of CBD is available. In order to determine the effects of CBD on sleep, it was administered intracerebroventricular (icv) in a dose of 10 μg/5 μl at the beginning of either the lights-on or the lights-off period. We found that CBD administered during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep were observed during the dark phase. Icv injections of CBD (10 μg/5 μl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus and dorsal raphe nucleus (DRD). Microdialysis in unanesthetized rats was carried out to characterize the effects of icv administration of CBD (10 μg/5 μl) on extracellular levels of dopamine (DA) within the nucleus accumbens. CBD induced an increase in DA release. Finally, in order to test if the waking properties of CBD could be blocked by the sleep-inducing endocannabinoid anandamide (ANA), animals received ANA (10 μg/2.5 μl, icv) followed 15 min later by CBD (10 μg/2.5 μl). Results showed that the waking properties of CBD were not blocked by ANA. In conclusion, we found that CBD modulates waking via activation of neurons in the hypothalamus and DRD. Both regions are apparently involved in the generation of alertness. Also, CBD increases DA levels as measured by microdialysis and HPLC procedures. Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.
AB - Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Δ9-THC modulates sleep, but no clear evidence on the role of CBD is available. In order to determine the effects of CBD on sleep, it was administered intracerebroventricular (icv) in a dose of 10 μg/5 μl at the beginning of either the lights-on or the lights-off period. We found that CBD administered during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep were observed during the dark phase. Icv injections of CBD (10 μg/5 μl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus and dorsal raphe nucleus (DRD). Microdialysis in unanesthetized rats was carried out to characterize the effects of icv administration of CBD (10 μg/5 μl) on extracellular levels of dopamine (DA) within the nucleus accumbens. CBD induced an increase in DA release. Finally, in order to test if the waking properties of CBD could be blocked by the sleep-inducing endocannabinoid anandamide (ANA), animals received ANA (10 μg/2.5 μl, icv) followed 15 min later by CBD (10 μg/2.5 μl). Results showed that the waking properties of CBD were not blocked by ANA. In conclusion, we found that CBD modulates waking via activation of neurons in the hypothalamus and DRD. Both regions are apparently involved in the generation of alertness. Also, CBD increases DA levels as measured by microdialysis and HPLC procedures. Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.
KW - Anandamide
KW - Cannabinoid receptor
KW - Dopamine
KW - Insomnia
UR - https://www.scopus.com/pages/publications/33746518572
U2 - 10.1016/j.febslet.2006.04.102
DO - 10.1016/j.febslet.2006.04.102
M3 - Artículo
C2 - 16844117
AN - SCOPUS:33746518572
SN - 0014-5793
VL - 580
SP - 4337
EP - 4345
JO - FEBS Letters
JF - FEBS Letters
IS - 18
ER -