- Background: Early life exposure to potentially traumatic experiences (PTEs) significantly increases the risk of responding more severely to stressful events experienced in adulthood. The aim of this study was to assess the autonomic nervous system (ANS) response to exposure to two PTEs in youth and again in adulthood, in terms of heart rate and heart rate variability in animals that responded to the PTE dramatically as compared to those that displayed virtually no behavioral response and to control animals. Methods: The prevalence of individuals displaying extreme anxiety-like behavioral responses to the PTE (predator urine or elevated platform) was assessed in the elevated plus-maze and startle response paradigms. Behavioral paradigms were complemented by assessment of the involvement of the ANS in relation to changes in behavior. Results: Juvenile trauma increases the vulnerability for developing long-term behavioral disruptions, taken to represent post-traumatic stress symptoms, after a second exposure to the same stressor in adulthood. PTSD-like behaviors and persisting physiological abnormalities resulted from disturbed recovery from the initial stress response. Conclusions: Exposure to a PTE during youth can have significant and long-lasting effects in adulthood and predispose the individual to PTSD upon subsequent re-exposure. Monitoring of ANS parameters confirms that development of extreme long-term (PTSD-like) behavioral changes is associated with a failure of recovery from the initial ANS responses to stress exposure.