Experimental posttraumatic stress disorder: the influence of early life stress and characterization of neural circuits

Abstract

Stress can be understood as the state of an organism aiming to reestablish its dynamic balance, which has been threatened or interrupted by physical or psychological factors. The experience of stress during early life, such as physical, emotional or sexual abuse, parental loss or neglect, and others, is associated with a higher risk of developing psychopathologies in adult life, as depression, anxiety disorders, drug abuse and posttraumatic stress disorder (PTSD). The PTSD is a psychopathology triggered by a traumatic event, and it is markedly characterized by intense anxiety, avoidance and hypervigilance responses. The PTSD symptoms appear to reflect stress-induced changes in the neurobiological systems and an inadequate response of these systems against severe stressors. Several factors seem to contribute to different levels of individual vulnerability or resilience to PTSD. This project proposal aims to assess if stress experienced during early periods of postnatal development is related to a greater behavioral response in an experimental PTSD model and to analyze neurobiological substrates that may be related to the etiology and course of the disorder. To do so, we will use an animal model of early life stress (ELS), in which there is an abnormal and fragmented maternal care, and we will evaluate the development of PTSD during adult life through a predator confront paradigm. The following outputs will be analyzed: a) effects of early life stress on behaviors associated with PTSD and b) neuronal activity (immunohistochemistry of the c-Fos protein and CRH peptide) in the brain, including hippocampus, paraventricular nucleus of the hypothalamus (PVN), periaqueductal gray (PAG) and amygdaloid nuclei. (AU)