Although DSI is mediated by eCB signaling in the BLA (Zhu and Lovinger, 2005), the identity of the eCB ligand remains unknown. We show that DSI is blocked by inhibition of DAGL with THL, indicating mediation by 2-AG. These findings are consistent with earlier data showing that DSI is typically mediated by 2-AG (see Kano et al, 2009 for review). We also show that blockade of MGL with MAFP prolongs DSI in the BLA, consistent with data from hippocampus (Hashimotodani et al, 2007b). Although MAFP also blocks fatty-acid amide hydrolase (FAAH), the enzyme that degrades another eCB anandamide, it is unlikely DSI is mediated by anandamide because the ability of MAFP to prolong DSI required DAGL activity. In addition, selective inhibitors of FAAH do not prolong DSI in other brain regions (Hashimotodani et al, 2007a).
