In adult animals, CRS, enhances eCB signaling in the amygdala which leads to habituation of the stress response by increasing inhibition of the HPA axis (Gorzalka and Hill, 2011). In contrast, CMS protocols lead to non-habituating activation of the HPA (Marin et al., 2007; Grippo and Johnson, 2009). The hippocampus contributes to both fast and delayed feedback inhibition of the HPA through a braking mechanism driven by glucocorticoid (GC) receptors (Jankord and Herman, 2008). Hippocampal excitatory output most likely drives GABAergic neurons in the ventral subiculum and thus provides an inhibitory influence on downstream HPA structures (Herman and Mueller, 2006; Jankord and Herman, 2008). Interestingly, acute stress enhances hippocampal DSI, resulting in a transient increase of excitatory hippocampal output from the CA1/subiculum region (Wang et al., 2011). This suggests that eCBs play an essential role in the hippocampal braking mechanism on the HPA axis. Moreover, this DSI enhancement is due to a GC-induced increase in 2-AG levels with a concomitant decrease in AEA levels (Wang et al., 2012); implicating eCB signalling at CCK-GABAergic terminals in the GC- negative feedback loop
