Effects of Intranasal NPY on Cardiovascular Parameters and Activity in SPS Model of PTSD: Telemetric Studies
Authors: Camp Robert L , Serova Lidia I , Stier Charles L , Sabban Esther L 
Published: June 2021

Single prolonged stress (SPS) is a rodent model of PTSD with high construct and face validity. Our previous studies revealed that early intervention with neuropeptide Y (NPY) delivered to the brain by intranasal pathways is very effective to prevent development of many of the SPS‐elicited impairments in behavioral and neuroendocrine functions, demonstrating its therapeutic potential. However, there are conflicting findings regarding the effect of NPY on the cardiovascular system. On one hand, NPY is co‐released with norepinephrine from the sympathetic nerve terminals in the periphery and can enhance norepinephrine's vaso constrictive effects. On the other hand several studies indicate that delivery of NPY to selective brain regions may elicit hypotensive effects.

Therefore, we examined whether intranasal NPY affects the major cardiovascular responses to SPS. Telemetric probes (TA11PA‐C40, Data Sciences) were implanted to measure blood pressure (BP), heart rate (HR) and activity in male Sprague Dawley rats. After recovery from the surgery data was collected every 10 min. When basal parameters were established, animals were subjected to SPS stressors and infused with 150 μg NPY or vehicle (water). They were returned to the receivers and data measured, every 2 min for 2 hrs and every 10 min subsequently for 6 days afterwards.

SPS stressors led to significant elevation of mean arterial pressure (MAP) and HR in all groups. MAP was elevated in both the vehicle and NPY treated group by (20.5 ±2.3 mHg, p=0.01; 25.7 ±6.1 mmHg, p<0.001 respectively) with no significant difference between them. The MAP returned towards basal levels by the following day; however MAP in the vehicle‐treated group MAP remained significantly elevated for several of the days following exposure to SPS stressors.

A large elevation in heart rate (HR) in response to SPS was observed in both groups. However, the elevation in the NPY treated group (116 ±5 bpm p<0.001) was significantly (p<0.05) lower than in the vehicle treated group (139 ±7 bpm, p<0.001). In the week following SPS stressors, the HR was similar to basal levels during the light phase, but lower than basal levels during the dark phase (normally active phase) with no difference between NPY‐ or vehicle‐treated groups.

SPS triggered pronounced effects on activity. In vehicle, but not NPY‐treated group, activity was elevated above basal levels immediately following exposure to SPS stressors. In the days following SPS, activity was significantly reduced from baseline in both groups, especially during the dark (normally active) phase. Dark phase activity gradually returned towards basal levels in the NPY group, and 6 days post‐SPS stressors was still depressed in the vehicle‐treated animals.

The results indicate that while intranasal NPY may be slightly beneficial for immediate changes in HR and long‐term effects on activity and MAP, overall it does not markedly alter the cardiovascular response to traumatic stress in animal model of PTSD.

Support or Funding Information

Supported by grant W81XWH‐16‐1‐0016 from US Army MOMRP