including the striatum, hippocampus, NAc, and amygdala (Vinod et al., 2008a). Together these results suggest that the increased levels of ECs following chronic ethanol may arise from enhanced synthesis and reduced inactivation mechanisms. However, to fully establish the causative role of the ethanol-induced increases in EC content as the mechanism responsible for down-regulation of CB1, studies utilizing genetic and pharmacological tools to block EC metabolism will need to be conducted. Unfortunately, the multiple pathways of AEA biosynthesis make the selective reduction of AEA a difficult task, so new methodologies will be required to advance our understanding of the molecular mechanisms associated with the EC systems role in ethanol tolerance.
