Sleep Resilience, Comorbid Anxiety, and Treatment in a Murine Model of PTSD

摘要

Sleep disturbances are an important pathway by which the negative effects of trauma exposure lead to PTSD and other psychological difficulties. Because it is difficult to test and control the effects of trauma exposure in humans, we have developed a novel mouse model of PTSD that is based on well-established paradigms of fear conditioning (FC). We specifically developed a conditioning stimulus of mild transient hypercapnia that we proposed could be used for re-exposure during periods of sleep. We have initially validated our model by showing that mice exhibit a marked bradycardia and changes in EMG activity with exposure to hypercapnia prior to foot shock (conditioned stimulus). We have gone on to show that the physiologic responses to the conditioning stimulus are dependent on genetic background. We have also been able to successfully re-expose conditioned animals to hypercapnia during sleep and again have shown genetic differences exist in the hyperarousal state that develops with re-exposure. These initial studies both validate our model and demonstrate that re-exposure of a conditioning stimulus during the unconscious state can produce or exacerbate and underlying state of hyperarousability.