withdrawal produce persistent changes in glucocorticoid signaling. CORT levels are known to remain elevated in brain tissue up to several months following chronic ethanol treatment even after circulating CORT has returned to basal levels (Little et al., 2008), and this persistent elevation in CORT may interact with CB1 expression and 2-AG levels along the lines observed following CUS. Other studies have implicated the EC system in dampening the stress response to an acute injection of ethanol (Cippitelli et al., 2008) and in mediating stress-induced drinking in mice (Racz et al., 2003). Additionally, the increased stress response during early phase of withdrawal is attenuated by acute injection of SR (Rubio et al., 2008). Given the data from studies of alcohol dependence in humans and in rodents that demonstrate altered functioning of the EC system, it seems likely that concomitant changes in glucocorticoid signaling may be involved. These data suggest that the interaction between stress, ethanol, and the EC system may be fruitful ground for new research.
