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 on HPA activity. This hypothesized braking mechanism could explain why certain types of repeated stress (i.e. unpredictable, heterotypic stressors) result in non-habituating GC responses. That is, following termination of a stressor, the “brake” would inhibit the GC response to sufficiently prevent habituation. This compensatory mechanism would enable an organism to regulate its responses to stress and respond appropriately to threatening and non-threatening stimuli. Thus, the GC-eCB hippocampal “brake” would be adaptively beneficial when encountering an acute or novel stressor; however, when exposed to unpredictable chronic stress, this mechanism could lead to excessive GC levels. While hippocampal HPA-inhibition appears to be mediated by the ventral hippocampus, basal circadian glucocorticoid secretion is regulated by the dorsal hippocampus (Herman and Mueller, 2006; Jankord and Herman, 2008). We observed that CB1 levels were significantly more downregulated in the dorsal compared to the ventral adult male hippocampus (Reich et al., 2009), indicating that CB1 signalling may regulate the glucocorticoid circadian rhythm. Conversely, the hippocampus can
