Neuropeptide Y (NPY) infusion attenuates development of PTSD‐like symptoms to traumatic stress in rats

Abstract

NPY has anxiolytic properties associated with resilience to stress‐related disorders, such as PTSD. However, due to its hypertensive effects, peripheral administration is undesirable, thus we used intranasal (IN) infusion. Rats were pretreated with single IN NPY or vehicle before exposure to single prolonged stress (SPS) animal model of PTSD and compared to untreated controls. Thirty min after SPS the elevation of plasma ACTH and corticosterone was not as pronounced in NPY‐infused rats and the induction of tyrosine hydroxylase (TH) in locus coeruleus (LC) was attenuated. Seven days after SPS, they displayed reduction in development of anxiety, depressive‐like behavior and hyperarousal. Plasma ACTH, corticosterone, and hippocampal glucocorticoid receptor levels were significantly above controls only in the vehicle, but not IN NPY‐treated. Baseline TH mRNA levels in LC did not differ among groups, but increased with forced swim in the vehicle‐, but not NPY‐pretreated animals. Administration of IN NPY immediately post‐SPS led to a similar reduction in PTSD associated behaviors. The results show that IN NPY can alter stress‐triggered dysregulation of the HPA axis and activation of central noradrenergic activity and provide proof of concept for potential of IN NPY as a non‐invasive prophylactic treatment or early intervention in response to traumatic stress. Supported by US army grant DM102881.