Activation of NPY receptor subtype 1 by [D-His <superscript>26</superscript> ]NPY is sufficient to prevent development of anxiety and depressive like effects in the single prolonged stress rodent model of PTSD.

The neuropeptide Y (NPY) system plays an important role in mediating resilience to the harmful effect of stress in post-traumatic stress disorder (PTSD). It can mediate its effects via several G-protein coupled receptors: Y1R, Y2R, Y4R and Y5R. To investigate the role of individual NPY receptors in the resilience effects of NPY to traumatic stress, intranasal infusion of either Y1R agonists [D-His 26 ]NPY, [Leu 31 Pro 34 ]NPY, Y2R agonist NPY (3-36) or NPY were administered to male Sprague-Dawley rats immediately following the last stressor of the single prolonged stress (SPS) protocol, a widely used PTSD animal model. After 7 or 14 days, effects of the treatments were measured on the elevated plus maze (EPM) for anxiety, in forced swim test (FST) for development of depressive-like or re-experiencing behavior, in social interaction (SI) test for impaired social behavior, and acoustic startle response (ASR) for hyperarousal. [D-His 26 ]NPY, but not [Leu 31 Pro 34 ]NPY nor NPY (3-36) Y2R, was effective in preventing the SPS-elicited development of anxiety. Y1R, but not Y2R agonists prevented development of depressive- feature on FST, with [D-His 26 ]NPY superior to NPY. The results demonstrate that [D-His 26 ]NPY was sufficient to prevent development of anxiety, social impairment and depressive symptoms, and has promise as an early intervention therapy following traumatic stress.

Competing Interests: Declaration of Competing Interest ELS: Provisional Patent Application No 62/819.820, “Intranasal Neuropeptides for Use in Stress-related Impairments”. All other authors have no potential competing interests. Author statement Chis Nwokafor: was involved in performance of the experiments, interpretations and writing the manuscript, Lidia Serova was involved in the conceptualization, performance and interpretation of some of the experiments, Roxanna Nahvi was involved in performance of some of the experiments and in preparing the manuscript, Jaclyn McCloskey was involved in performance and interpretation of some of the experiments, Esther L Sabban was involved in conceptualization, planning, analysis and writing the manuscript.

(Copyright © 2019. Published by Elsevier Ltd.)