Abstract: The present invention relates to a method for preventing or treating pathological conditions associated with intense stress such as Post-Traumatic Stress Disorder (PTSD) by targeting the endogenous PAI-1 (Type 1 Plasminogen Activator Inhibitor). In the present invention, inventors demonstrate that there is a shift in the balance between the expression of tPA and PAI-1 proteins in a hippocampal region of a preclinical model of Post-Traumatic Stress (PTSD), is responsible for the transition between moderate stress which increases memory and facilitates adaptation and intense stress intense stress which induce pathological memories. In conditions of moderate stress, glucocorticoid hormones (GC) increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2MAPK cascade strengthens memory. When stress is particularly intense, very high levels of GC then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories.