Effect of chronic ethanol exposure and its withdrawal on the endocannabinoid system

The present study investigated the effect of ethanol (EtOH) exposure and its withdrawal on the central endocannabinoid system utilizing an EtOH vapor inhalation model, which is known to produce functional tolerance and dependence to EtOH. Swiss Webster mice (n = 24) were exposed to EtOH vapors for 72 h. Mice were sacrificed after 72 h following EtOH exposure (n = 12) and 24 h after its withdrawal (n = 12). Radioligand binding assays were performed to measure the density of CB1 receptor and CB1 receptor agonist-stimulated [35S]GTPγS binding in crude synaptic membranes isolated from the cortex, hippocampus, striatum and cerebellum. The density of CB1 receptor was significantly decreased (31–39%) in all the brain regions when compared to the control group. The CB1 receptor-stimulated Gi/o protein activation was also found to be decreased (29–40%) in these brain regions of EtOH exposed mice. Recovery of the CB1 receptor density, in addition to, the CB1 receptor-mediated G-protein activation was observed after 24 h withdrawal from EtOH. The levels of cortical anandamide, which was significantly increased (147%) by EtOH exposure, returned to basal levels after 24 h of withdrawal from EtOH exposure. A significant reduction (21%) in the activity of fatty acid amide hydrolase was found in the cortex of EtOH administered mice. Taken together, the neuroadaptation in the EC system may have a potential role in development of tolerance and dependence to EtOH.