The neuronal eCB signaling system is composed of eCB ligands, including 2-AG and anandamide, their synthetic and catabolic enzymes, and CB1 receptors (Kano et al, 2009; Piomelli, 2003). 2-arachidonoylglycerol (2-AG) is the most abundant eCB found in brain, and is synthesized in response to Gq-coupled receptor activation or calcium influx, from sn-2 arachidonic acid (AA) containing diacylglycerol (DAG) precursors (Jung et al, 2005, 2007). This synthetic reaction is catalyzed by DAG lipase (DAGL), which is expressed within postsynaptic neuronal elements (Katona et al, 2006; Uchigashima et al, 2007). On synthesis, 2-AG diffuses to presynaptic axon terminals where it activates CB1 receptors to reduce GABA and glutamate release (Kano et al, 2009). 2-AG is then degraded by presynaptically located monoglyceride lipase (MGL), to free AA and glycerol (Ahn et al, 2008). This form of retrograde eCB signaling has been studied in several brain regions implicated in the regulation of memory and emotion including the amygdala (Azad et al, 2004; Marsicano et al, 2002; Zhu and Lovinger, 2005).
