The present findings likely generalize and extend beyond the regulation of the HPA axis. Amygdalar endocannabinoid signaling is important for adaptive emotional flexibility (Marsicano et al., 2002; Lin et al., 2006), such as fear extinction, which is disrupted by stressful stimuli (Izquierdo et al., 2006; Miracle et al., 2006; Holmes and Wellman, 2009; Baran et al., 2009). Specifically, AEA signaling within the amygdala mediates forms of synaptic plasticity, such as inhibitory long-term depression, which are conducive to fear extinction and emotional flexibility (Azad et al., 2004). Accordingly, it is possible that stress-induced reductions in AEA/CB1 receptor signaling in the BLA contribute to the alterations in emotional reactivity and flexibility elicited by exposure to stressful stimuli.
