Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: An effect abolished by a single amphetamine injection

•Some traumatized rats develop PTSD symptoms while others are resilient.•These susceptible rats avoided trauma-related stimuli, as PTSD subjects.•A single amphetamine injection delivered in trauma context abolished PTSD symptoms.•Positive mood combined with trauma memory reactivation induce memory remodeling. The present study had two main goals. First, to investigate whether an animal model of post traumatic stress disorder (PTSD), single prolonged stress (SPS) leads to one of the main PTSD symptom: avoidance of trauma-related stimuli. Second, to investigate whether a single amphetamine injection delivered 30 days after SPS can reduce these symptoms. Olfactory and auditory cues were added to the SPS context and reactivity to these cues were tested more than one month later using an odor discrimination test, and freezing to the trauma-related tone. Other PTSD symptoms, such as anxiety (elevated plus maze) and hyperarousal (acoustic startle response), were also investigated in these rats. Some behavioural reactivity to the environmental cues was observed in rats exposed to SPS. However, a subgroup of these rats showed an exaggerated disruption in performance in 3 to 4 of the behavioral tests relative to controls, suggesting that two classes of rats, those that are susceptible and those that are resilient to SPS, can be dissociated. When rats were treated with amphetamine (1mg/kg) injected in the SPS context 30 days after SPS, traumatized rats no longer differed from their corresponding controls and all were identified as resilient. The present data demonstrated that rats exposed to SPS can be either susceptible or resilient and a single amphetamine injection can abolish the associated symptoms. We propose that combining memory reactivation, with an amphetamine-induced positive mood, can modify the emotional valence of the initial memory, inducing long-lasting remodeling of the traumatic memory, thereby opening a novel therapeutic avenue.