RT Journal Article
SR Electronic
T1 Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 901
OP 910
DO 10.1523/JNEUROSCI.1647-20.2020
VO 41
IS 5
A1 Paul J. Marvar
A1 Raül Andero
A1 Rene Hurlemann
A1 Tiffany R. Lago
A1 Moriel Zelikowsky
A1 Joanna Dabrowska
YR 2021
UL http://www.jneurosci.org/content/41/5/901.abstract
AB 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.