Collectively, these data create an emerging picture of differential roles of the endocannabinoid ligands AEA and 2-AG in the neurobehavioral responses to stress. An induction of 2-AG in response to stress throughout the forebrain may contribute to both constraining neuronal activation and HPA axis activity as well as drive behavioural changes such as ethanol consumption and suppression of sexual behaviour. On the other hand, a reduction in AEA signalling may disinhibit neuronal activity in limbic-hypothalamic structures and promote HPA axis activation and changes in emotional behaviour and neuroplasticity. While time course studies have not been properly performed in this regard, there may be a temporal nature to these changes such that the decline in AEA happens relatively rapidly following stress exposure to promote immediate responses to aversive environmental stimuli (increased HPA axis activity and emotional reactivity), while the increase in 2-AG occurs at a later time point and is more involved in the termination of the stress response and a return to homeostasis.
