Repeated fear‐induced diurnal rhythm disruptions predict PTSD‐like sensitized physiological acute stress responses in F344 rats

Abstract

To identify objective factors that can predict future sensitized stress responses, thus allowing for effective intervention prior to developing sensitization and subsequent stress-related disorders, including post-traumatic stress disorder (PTSD). Adult male F344 rats implanted with biotelemetry devices were exposed to repeated conditioned fear or control conditions for 22 days followed by exposure to either no, mild or severe acute stress on day 23. Diurnal rhythms of locomotor activity (LA), heart rate (HR) and core body temperature (CBT) were biotelemetrically monitored throughout the study. In a subset of rat not implanted, corticosterone and indices of chronic stress were measured immediately following stress. Rats exposed to repeated fear had fear-evoked increases in behavioural freezing and HR/CBT during exposure to the fear environment and displayed indices of chronic stress. Repeated fear produced flattening of diurnal rhythms in LA, HR and CBT. Repeated fear did not sensitize the corticosterone response to acute stress, but produced sensitized HR/CBT responses following acute stress, relative to the effect of acute stress in the absence of a history of repeated fear. Greater diurnal rhythm disruptions during repeated fear predicted sensitized acute stress-induced physiological responses. Rats exposed to repeated fear also displayed flattened diurnal LA and basal increases in HR. Exposure to repeated fear produces outcomes consistent with those observed in PTSD. The results suggest that diurnal rhythm disruptions during chronic stressors may help predict sensitized physiological stress responses following traumatic events. Monitoring diurnal disruptions during repeated stress may thus help predict susceptibility to PTSD.