Modeling of Post-Traumatic Stress Disorder in Mice: Nonlinear Relationship with the Strength of the Traumatic Event
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The neurophysiological mechanisms of the development of post-traumatic stress disorder (PTSD) in humans remain poorly understood and require experimental investigation in animal models. We report here studies of variation in the range of conditions for the acquisition of PTSD in a learned fear model in mice using electrocutaneous shocks (ECS) as the stressful event. Use of different ECS application parameters showed that the severity of fear-induced and behavioral sensitization has a nonlinear relationship with the intensity of the traumatizing event. The optimum parameters for acquisition of PTSD are three shocks each of current 1.5 mA and duration 10 sec. The critical parameter is the number of ECS applied. Increases in the strength or duration of the traumatizing event did not lead to more severe signs of PTSD. As the number of ECS increased further, the behavior of the mice stopped being homogeneous: some of the animals demonstrated marked PTSD-like behavior, while others showed no signs of PTSD at all. These results identify the effective conditions for acquisition of PTSD in a learned fear model in mice and the conditions for the occurrence of individual variability in the traumatizing event, points important for understanding the mechanisms forming PTSD.
Keywordspost-traumatic stress disorder stress psychological trauma animal models conditioned reflex fear memory sensitization anxiety individual differences
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