Post-traumatic stress disorder (PTSD) is a multifaceted psychological disorder characterized by deregulated fear and stress responses. Etiology and progression of PTSD involve multiple neurochemical factors that interact in complex ways and consequently alter range of neurotransmitters systems. One of the most important is CRH system, which involvement in fear and stress response is well established. CRH acts through two receptors, CRHR1 that plays role in stress responding and anxious arousal and CRHR2 that is responsible for dampening the stress response initiated by activation of CRHR1. In our experiment we altered CRHR2 signaling pathway by intranasal administration of Ucn2 a Ucn3 and thus affect the mechanism leading to development of negative behavioral outcomes in animal model of PTSD. Animals exposed to Single Prolonger Stress (SPS) animal model of PTSD were intranasaly administered saline, Ucn2 or Ucn3 and after 7-day habituation were tested in the EPM and OF. Afterwards animals were decapitated. In the OF we observed positive effect of Ucn3 administration on PTSD behavioral manifestations compared to "PTSD" animals. We have saw slight changes in blood corticoid levels after Ucn3 treatment. Moreover in PVN of PTSD animals we found increased gene expression of CRH not seen after Ucn3 treatment. In addition Ucn3 application led to significant increase of FKBP5 gene expresion in PVN compared to PTSD animals. Our preliminary data shows that CRHR2 signaling pathway may be a potential target of interest to study mechanisms of stress response mechanisms in animal model of PTSD.Grant support: VEGA 2/0010/22, VEGA2/0050/23.