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Updated: Jun 21, 2026
Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis
Published on: March 28, 2018
Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
Iddo Magen1, Yosefa Avraham, Zvi Ackerman
1Department of Human Nutrition and Metabolism, Braun's School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel.
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 (5mg/kg; i.p.) was administered over 4weeks 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-alpha-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-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.
Conclusions:
The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.
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