Lateral Septal PACAP Signaling Modulates Stress and Anxiety in Rodent Models

Anxiety and trauma-related disorders represent a significant global health burden, often characterized by maladaptive physiological responses to environmental stressors [1]. While traditional pharmacotherapy often targets monoamine systems, emerging research highlights the role of neuropeptides in fine-tuning the neural circuitry of emotion and fear processing [2]. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved peptide, has been increasingly linked to the regulation of the hypothalamic-pituitary-adrenal axis and the development of post-traumatic stress disorder [3]. Specific pathways involving PACAP receptors are now known to mediate complex behaviors ranging from panic-like symptoms to social avoidance [4, 5]. A new study now offers fresh insights into how localized signaling of this peptide within the limbic system dictates the transition between active and passive stress-coping strategies.