Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

• Published in: The Journal of neuroscience Vol. 41; no. 5; pp. 901 - 910
• Main Authors: Marvar, Paul J., Andero, Raül, Hurlemann, Rene, Lago, Tiffany R., Zelikowsky, Moriel, Dabrowska, Joanna
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 03.02.2021
• Subjects: Aggressive behavior; Angiotensin; Angiotensin II; Angiotensin receptors; Animals; Anxiety; Anxiety - drug therapy; Anxiety - metabolism; Anxiety - psychology; Defensive behavior; Drug therapy; Emotions - drug effects; Emotions - physiology; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fear; Fear conditioning; Humans; Limbic System - drug effects; Limbic System - metabolism; Mental disorders; Modulators; Nerve Net - drug effects; Nerve Net - metabolism; Neuromodulation; Neuropeptides; Neuropeptides - metabolism; Neuropeptides - pharmacology; Neuropeptides - therapeutic use; Oxytocin; Oxytocin receptors; Post traumatic stress disorder; Psychological stress; Receptors; Receptors, Tachykinin - antagonists & inhibitors; Receptors, Tachykinin - metabolism; Signs and symptoms; Stress Disorders, Post-Traumatic - drug therapy; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - psychology; Symposium/Mini-Symposium; Tachykinin; Tachykinin receptors; Tachykinins - antagonists & inhibitors; Tachykinins - metabolism; Trauma; Vasopressin; PTSD; anxiety; oxytocin; angiotensin II; vasopressin; tachykinin
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.1647-20.2020

Post-traumatic stress disorder (PTSD) is characterized by hypervigilance, increased reactivity to unpredictable versus predictable threat signals, deficits in fear extinction, and an inability to discriminate between threat and safety. First-line pharmacotherapies for psychiatric disorders have limited therapeutic efficacy in PTSD. However, recent studies have advanced our understanding of the roles of several limbic neuropeptides in the regulation of defensive behaviors and in the neural processes that are disrupted in PTSD. For example, preclinical studies have shown that blockers of tachykinin pathways, such as the Tac2 pathway, attenuate fear memory consolidation in mice and thus might have unique potential as early post-trauma interventions to prevent PTSD development. Targeting this pathway might also be beneficial in regulating other symptoms of PTSD, including trauma-induced aggressive behavior. In addition, preclinical and clinical studies have shown the important role of angiotensin receptors in fear extinction and the promise of using angiotensin II receptor blockade to reduce PTSD symptom severity. Additional preclinical studies have demonstrated that the oxytocin receptors foster accurate fear discrimination by facilitating fear responses to predictable versus unpredictable threats. Complementary human imaging studies demonstrate unique neural targets of intranasal oxytocin and compare its efficacy with well-established anxiolytic treatments. Finally, promising data from human subjects have demonstrated that a selective vasopressin 1A receptor antagonist reduces anxiety induced by unpredictable threats. This review highlights these novel promising targets for the treatment of unique core elements of PTSD pathophysiology.