Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation☆
Received 12 August 2008; received in revised form 18 March 2009; accepted 6 April 2009. published online 27 May 2009.
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-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.
☆ The authors who have taken part in the study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.
ABSTRACT