Mood disorders such as major depressive disorder are serious mental illnesses that affect approximately 20% of Americans (Kessler et al., 2010). The cannabinoid receptor, CB1 and its ligands, the endocannabinoids (eCBs), are intricately involved in the stress response (Gorzalka and Hill, 2011; Hill et al., 2010) and are therefore putative contributors to the etiology of depressive disorders. Martin et al., (2002) first demonstrated that mutant mice deficient in CB1 receptors show an enhanced vulnerability to the depressive effects of a chronic mild stress protocol (CMS), a valid preclinical model of depression (Willner, 2005). Buttressing this finding, three-week exposure to a similar chronic mild stress protocol produced a ~50% reduction in CB1 levels in several limbic structures including the hippocampus (Hill et al., 2005, 2008b; Reich et al., 2009). Exposure to both chronic mild stress and chronic restraint stress consistently reduces the endocannabinoid/endovanniloid, Anandamide (AEA), in the hippocampus, amygdala, striatum, medial prefrontal cortex and hypothalamus (Gorzalka and Hill, 2011). Conversely, the other major endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), is transiently enhanced by chronic or acute restraint stress but is either reduced or
