Amygdalar corticotropin-releasing factor mediates stress-induced anxiety.

The extended amygdala, including the Central nucleus of the Amygdala (CeA) and the Bed Nucleus of the Stria Terminalis (BNST), is a complex structure that plays a pivotal role in emotional behavior. The CeA and the BNST are highly interconnected, being the amygdala traditionally more associated with fear and the BNST with anxiety. Yet, studies using excitotoxic lesions also show the involvement of the CeA in the development of stress-induced anxiety. Likewise, others have also highlighted the role of corticotropin-releasing factor (CRF), a neuropeptide highly expressed in CeA, as an anxiogenic factor and, consequently, important for in anxiety disorders. Here, we used an inducible RNAi lentiviral system to assess the effects of reducing CRF expression in CeA in the development of anxiety-like behavior in a model of Chronic Unpredictable Stress. In addition, we evaluated CRF RNAi-mediated alterations in the stress-triggered molecular signature in the BNST. Knockdown of CRF in the CeA decreased stress-induced anxiety levels. No differences were found in a fear-potentiated startle paradigm. Additionally, we observed that stress-induced alterations in the expression of CRF receptors within the BNST are attenuated by CRF knockdown in the CeA. These results emphasize the importance of the role that amygdalar CRF plays in the modulation of anxiety-like behavior and in the molecular signature of stress in the BNST.