The fact that stress increases 2-AG and decreases AEA, while corticosterone predominately increases AEA, with 2-AG elevations only being detected in the hypothalamus, suggests that the effects of stress and glucocorticoids on 2-AG and AEA content are likely mediated through distinct mechanisms. With respect to AEA, one possibility is that stress (through changes in neurotransmission or excitability that precedes activation of the HPA axis) decreases AEA content, and that glucocorticoids increase AEA content in an attempt to normalize AEA signaling following stress. This hypothesis is in line with the role of glucocorticoids to reinstate homeostasis in circuits that have been disrupted by stress.
