Prolonged fear incubation leads to generalized avoidance behavior in mice

Abstract Long-lasting presence of avoidance and emotional numbing are reliable behavioral markers for PTSD, but little is known about its psychological and biological underpinnings. We employed our recently established mouse model of PTSD (i) to study the emergence of avoidance behavior in the aftermath of a trauma, (ii) to disentangle the impact of context generalization vs. lack of motivation vs. novelty fear and (iii) to assess the therapeutic value of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Specific conditioned avoidance to shock-paired odor turned into generalized avoidance after 28 days of fear incubation. Combination of habituation to the novel environment and extinction of contextual fear abolished both generalized and specific avoidance behavior. Chronic fluoxetine treatment partially reversed the phenotype, whereas acute treatment with diazepam did not. Our animal model may help understanding the mechanisms underlying psychological and biological mechanisms of PTSD for the benefit of developing pharmacotherapeutic strategies, which specifically address generalized avoidance.