Sensitivity to Trauma-associated Cues is Restricted to Vulnerable Traumatized Rats and Reinstated After Extinction by Yohimbine

While post-traumatic stress disorder (PTSD) symptom is mainly characterized by re-experiencing the traumatic event, the reactivity to trauma-associated cues in resilient and vulnerable subjects has not been extensively studied. Using an animal model of PTSD induced by a single prolonged stress (SPS), the responses of traumatized Vulnerable and Resilient rats to PTSD-like symptom tests and to trauma-associated cues were investigated. In addition, the implication of the noradrenergic system in "re-experiencing" was explored. Rats received either a SPS, combining a 2h restraint stress, a 20min forced-swim followed by a 15min rest, and a loss of consciousness produced by inhaling CO2 emissions, delivered in the presence of particular cues (tone and odor), or a control procedure. PTSD-like symptoms and reactivity to various trauma-associated cues (specific, contextual, or predictive) were tested from D15 to D60 after the SPS. Rats were then divided into Resilient and Vulnerable on the basis of three main symptom tests, including the elevated plus maze, the light-dark and the acoustic startle response tests. Although Resilient rats behaved like Controls rats, Vulnerable rats developed long-term PTSD-like symptoms on the main symptoms tests (anxiety and alteration of arousal), as well as other PTSD-like outcomes (such as anhedonia and avoidance to trauma-associated cues). These Vulnerable rats were also the only ones to demonstrate strong reactivity to trauma-associated cues. In addition, the alpha-2 adrenergic receptor antagonist, Yohimbine (i.p., 1.5mg/kg/ml), was able to reinstate fear responses to an extinguished trauma-associated odor. Our results established clear relationships between Vulnerability to trauma and reactivity to trauma-associated cues and further suggest an involvement of the noradrenergic system.