Notwithstanding, several recent observations demonstrate that loss of AEA–CB1R signaling in the BLA can trigger behavioral and neuroendocrine responses to stress. First, presumably by removing AEA-mediated tonic inhibitory activity, CB1R antagonism increases BLA excitability [61–63], activates the hypothalamic–pituitary–adrenal (HPA) axis and increases anxiety-like behavior [58,64,65]. Second, increasing AEA by inhibiting FAAH (with URB597) reduces the HPA axis and anxiety-like response to stress [58,66]. These actions of FAAH inhibition have been localized to actions specifically within the BLA by the finding that only infusion of URB597 into the BLA, and not CeA or medial amygdala, is effective in producing these anti-stress effects [58]. Collectively, these findings support a model in which stress rapidly mobilizes FAAH, depletes the signaling pool of AEA, and increases BLA excitability to drive anxiety [67] (Figure 1).
