Psychological stress is hypothesized to activate the HPA axis through a top down process wherein the HPA axis is activated by a complex network of afferents arising from the limbic forebrain (Pecoraro et al., 2006; Herman et al., 2003; Sawchenko et al., 2000). Within this circuit, the amygdala has been identified as a primary site providing excitatory drive to the HPA axis (Herman et al., 2005). The present findings suggest that endocannabinoid signaling is integrated into this circuit such that stress dampens AEA/CB1 receptor signaling within the BLA, which in turn modulates the magnitude of HPA axis responses to stressful stimuli. This process, and ability of CB1 receptors to inhibit glutamate release from excitatory afferents, suggests a model by which tonic AEA within the BLA produces steady-state activation of the CB1 receptor and results in tonic inhibition of corticothalamic sensory afferents to the BLA. The application of a psychological stressor results in increased FAAH activity, which reduces AEA/CB1 receptor signaling, and disinhibits excitatory transmission in the BLA. As a result, the neural activity of BLA projection neurons that indirectly communicate
