The mechanisms underlying the pro-extinction effects of BLA–FAAH inhibition remain to be elucidated. One notable finding is that a CB1R-dependent form of synaptic plasticity in BLA [51,86], long-term depression of inhibitory GABAergic transmission (LTDi), is enhanced by FAAH KO [51] and by the FAAH inhibitor AM3506 at doses that promote extinction [50]. This suggests a scheme in which AEA released during extinction relieves a tonic inhibitory brake on BLA output neurons [50,51,86] necessary for the encoding of extinction memories [102] (Figure 2). However, it would be premature to discount the involvement of other mechanisms, including more direct effects on glutamatergic transmission, and this remains a key question for future work.
