Our data suggest that FAAH inhibition targets endogenous anandamide signaling in extinction circuitry. To further interrogate this hypothesis, we assessed whether AM3506 treatment augmented anandamide levels in brain regions mediating fear extinction. Mice underwent conditioning and extinction training as above. AM3506 was injected intraperitoneally 1 h before extinction and mice were killed immediately after extinction. The tissue was extracted from two key nodes within the extinction circuit—the BLA and ventromedial prefrontal cortex,13 as well as the dorsal striatum (as a control) (Figure 2a). Anandamide and 2-arachidonoylglycerol levels were quantified using liquid chromatography tandem mass spectrometry.33
