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 also enhance HPA activity (Herman and Mueller, 2006; Jankord and Herman, 2008), consequently an increase in hippocampal output, as observed here, could increase HPA activation. Dysfunction in any of these mechanisms may lead to prolonged, excessive or improperly-timed glucocorticoid secretion which, in turn, may damage the hippocampus and other HPA associated structures, resulting in stress-related pathologies such as anxiety, depression and PTSD. Thus, further elucidation of how endocannabinoids modulate the hippocampal-regulation of the HPA axis is necessary for understanding the etiology of stress-related mental disorders.
