TY - JOUR
T1 - Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
AU - Magen, Iddo
AU - Avraham, Yosefa
AU - Ackerman, Zvi
AU - Vorobiev, Lia
AU - Mechoulam, Raphael
AU - Berry, Elliot M.
PY - 2009/9
Y1 - 2009/9
N2 - Background/Aims: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease. Methods: CBD (5 mg/kg; i.p.) was administered over 4 weeks to mice that had undergone BDL. Results: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-α-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-α receptor 1 expression were blocked by ZM241385, an A2A adenosine receptor antagonist. BDL lowers the expression of this receptor. Conclusions: The effects of BDL apparently result in part from down-regulation of A2A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.
AB - Background/Aims: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease. Methods: CBD (5 mg/kg; i.p.) was administered over 4 weeks to mice that had undergone BDL. Results: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-α-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-α receptor 1 expression were blocked by ZM241385, an A2A adenosine receptor antagonist. BDL lowers the expression of this receptor. Conclusions: The effects of BDL apparently result in part from down-regulation of A2A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.
KW - Activity
KW - Bile duct ligation
KW - Cognition
KW - Gene expression
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=68049129534&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2009.04.021
DO - 10.1016/j.jhep.2009.04.021
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C2 - 19596476
AN - SCOPUS:68049129534
SN - 0168-8278
VL - 51
SP - 528
EP - 534
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -