It is also possible that the effects of endocannabinoid signaling in the BLA on the HPA axis are not be due to modulation of the CRH-ACTH pathway originating in the PVN, but instead are due to action on the autonomic arm of the stress axis. Specifically, it is possible that changes in amygdalar neuronal activity could affect principal autonomic relay nuclei, such as the brainstem and regions of the PVN which exhibit projections to autonomic spinal regions, which in turn could affect corticosterone secretion at a different peripheral level, either via changes in adrenal cortical cell sensitivity to ACTH or in hepatic blood flow to inhibit corticosterone clearance from the circulation. While this pathway could account for the modest effect size that is seen following modulation of endocannabinoid signaling in the BLA, it seems less plausible given that the BLA, as well as the MeA, through which the BLA is believed to communicate under conditions of psychological stress(Herman et al., 2005; Ulrich-Lai and Herman, 2009), exhibit little to no projections to the primary autonomic output nuclei (Ulrich-Lai and Herman, 2009).
