The contribution of BLA 2-AG to stress responsivity and recovery remains, in contrast to FAAH–AEA signaling, much less certain at the present time. As noted above, stress increases 2-AG in the BLA, which could suggest a protective/restorative role to counter the effects of stress-induced AEA depletion. In this context, systemically administered MAGL inhibitors have been shown to acutely reduce anxiety-like behavior [75–78], and when administered chronically, to prevent chronic stress-induced increases in anxiety-like behavior and impairments in BLA synaptic plasticity [75]. Further studies will be needed to determine the role of MAGL–2-AG signaling in moderating stress and the manner in which this mechanism interacts with the FAAH–AEA system in the BLA. Indeed, these relationships may be further complicated by sex differences in the ECB system and ECB mediation of anxiety (Box 2).
