Effects of multiple brief exposures to trauma-associated cues on traumatized resilient and vulnerable rats

• 4 exposures to a same trauma-cue durably increased anxiety and arousal in SPS rats
• 8 exposures to trauma cues (same or different) did not affect PTSD-like symptoms
• Vulnerable rats showed slower extinction to trauma-cues than Resilient rats
• A reminder stress can reinstate fear responses to a trauma-odor in Vulnerable rats
• Re-experiencing alone is not responsible for PTSD development.

Intrusive re-experiencing of a trauma is a core symptom in post-traumatic stress disorder (PTSD), and is often triggered by contextual cues associated with the event. It is not yet established if intrusive re-experiencing is the consequence of PTSD, or if it could contribute to the development of PTSD following a traumatic event. The present study (1) examined the impact of repeated brief re-exposures to trauma reminders on the strength of PTSD-like symptoms, as well as on their time-development and (2) investigated the reactivity over time to these cues in trauma resilient and vulnerable rats, defined on the basis of the PTSD-like symptoms they demonstrated.Rats were exposed to a Single Prolonged Stress, combining three different stresses (2-h restraint, 20-min forced swim and CO2 unconsciousness) delivered together with tone and odor cues and preceded by an inhibitory avoidance conditioning or a control procedure. During the following two weeks, reminded rats were briefly re-exposed to trauma-associated cues either 4 or 8 times.The results indicated that 4 re-exposures to the same cue strengthened PTSD-like symptoms (anxiety, arousal, fear to trauma-cue). However 8 re-exposures to similar or different trauma-cues did not alter PTSD-like symptoms and led to a rapid extinction of the fear reactivity to these cues. The present results further indicated that shortly after trauma, both resilient and vulnerable rats strongly reacted to trauma-associated cues, while only vulnerable rats reacted long after the trauma, suggesting a slower loss of fear responses to trauma cues in these rats.We concluded that re-experiencing may participate in, but cannot be solely responsible for, the development of long-term PTSD effects.