A large and growing body of evidence indicates that the EC system is involved in mediating the response to stress. For instance, activation of a novel, non-genomic glucocorticoid receptor in the hypothalamus produces an EC-mediated reduction in glutamate EPSCs on parvocellular neurons of the paraventricular nucleus, and this provides feedback inhibition along the hypothalamic-pituitary-adrenal axis (Di et al., 2003; Di et al., 2005; Di et al., 2009). Additionally, chronic treatment with glucocorticoid receptor agonists is associated with decreased levels of 2-AG and CB1 in the hippocampus (Hill et al., 2008), and similar findings are also observed in a rodent model of chronic unpredictable stress (CUS) that results in a persistent increase in circulating levels of corticosterone (CORT; Hill et al., 2005). Furthermore, stress is one of the predominant causes associated with relapse to alcohol abuse, and chronic ethanol treatment and 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
