Other evidence derives from the use of a fatty acid amide hydrolase (FAAH) inhibitor or inhibitor of reuptake of eCBs. Chronic administration of the FAAH inhibitor URB597, which would increase AEA levels, has been shown to reduce anxiety-like effects and to display antidepressant-like actions in a CUS rat model; effects that were prevented by a CB1R-selective antagonist SR141761A [106]. This effect was not always observed [107], as URB597, an irreversible FAAH inhibitor, failed to demonstrate antidepressant-like actions in either the FST or TST. The use of other FAAH inhibitors or the use of FAAH gene deletion (FAAH-KO) model mouse, however, showed clearly that inhibition (or ablation) of FAAH was anxiolytic and anti-depressive (reviewed in [68]). These results are corroborated by the use of an inhibitor for eCB uptake, AM404. Accumulation of eCBs following administration of the uptake inhibitor AM404 elicited an antidepressant-like effect, presumably by indirect stimulation of the CB1 receptors by eCBs [68].
