A key mechanism governing CB1R-mediated signaling is the active degradation of released ECBs. 2-AG is degraded presynaptically by monoacylglycerol lipase (MAGL). By contrast, the catabolic fate of a number of the N-acylethanolamine (NAE) group of ECBs, including N-palmitoyl ethanolamine (PEA) [39], N-oleoyl ethanolamine (OEA), and AEA [40], was suspected to be controlled by a common enzyme as early as 1984 [41]. This enzyme was later identified as the serine hydrolase enzyme, FAAH [42–44], which was then isolated and cloned and shown to be located postsynaptically [45]. In the rodent brain, the distribution of FAAH overlaps closely with CB1R in many but not all regions. Within amygdala subnuclei, FAAH is highly expressed on pyramidal neurons in the BLA, and to a significantly lesser extent in the central nucleus (CeA) [19,20,46,47]. Although activation of CB1R in the BLA causes a decrease in both glutamatergic and GABAergic transmission, there is typically a net reduction in neuronal excitability on application of CB1R agonists, probably due to CB1R-mediated presynaptic inhibition of glutamate release [48,49]. By contrast, CB1R signaling generated by increased AEA can also produce long-term depression of inhibitory transmission in the BLA, a change in synaptic plasticity which can serve to promote excitability [50,51].
