Remote fear memory is sensitive to reconditioning.

Highlights • Mice with remote fear memory are sensitive to original and novel reconditioning. • Reconditioning in an original fearful context causes remote fear memory resistance. • Reconditioning in a novel context produces more fear reactions in mice with remote fear memory. • Stress sensitivity of remote fear may be induced by fear memory system consolidation over time. Abstract Exposure of some individuals to recurring traumatic events from the same perpetrator or situation, such as during child abuse or domestic violence, is quite prevalent. Studies have shown that the number of traumatic events experienced is positively related to the severity of post-traumatic stress disorder and other mental disorders. Using a contextual fear conditioning (Cond1) and reconditioning (Cond2) paradigm, which were separated by either 1 or 35 days, we examined fear responses to immediate extinction and retrieval-extinction procedures after repeated fear conditioning stress. Based on the time interval between Cond1 and Cond2, the animals were divided into recent and remote fear memory groups. We observed that when Cond2 was performed in the original conditioning context in which Cond1 was performed, the reconditioned remote fear memory was resistant to the disruptive effect of immediate extinction and retrieval-extinction paradigms. Furthermore, the resistance to disruptive effects could be induced by very low shock intensities, which cannot even induce any fear response in naive animals. When Cond2 was performed in a novel context, animals with remote fear memory acquired a significantly higher fear response to the novel context. Our findings suggest that remote fear memory may be more sensitive to reconditioning and resistant to post-reconditioning disruption. [ABSTRACT FROM AUTHOR]