A growing body of evidence indicates that CB1 receptor agonists reduce anxiety-like behavior (Moreira et al., 2009). The high levels of CB1 receptor expression in the amygdala, hippocampus, hypothalamus, and prefrontal cortex (Mackie, 2006), coupled with evidence that CB1 receptor activation results in decreased release of glutamate and GABA (Steiner and Wotjak, 2008), support the idea that cannabinoids affect anxiety and anxiety-like behavior. FAAH inhibition, as well as genetic deletion of FAAH, have been reported to reduce anxiety-like behavior in the elevated plus maze (Moreira et al., 2008; Naidu et al., 2007; Patel and Hillard, 2006), zero maze (Kathuria et al., 2003), and light/dark box (Moreira et al., 2008), particularly under stressful conditions (Haller et al., 2009). However, investigation of the consequences of elevating endogenous 2-AG levels has not been possible until the recent development of the highly selective MAGL inhibitor, JZL184 (Long et al., 2009). Thus, little is known about the possible anxiolytic and/or anxiogenic effects of 2-AG modulation in vivo.
