Re-exposures in the Dark Cycle Promote Attenuation of Fear Memory: Role of the Circadian Cycle and Glucocorticoids.

• Reactivation in the dark cycle attenuates fear memory expression within session, but not in the test. • Successive fear reactivations in the dark cycle update memory, attenuating freezing expression. • Fear reduction through reactivations in the dark cycle is mediated by glucocorticoid. It has been shown that a previously consolidated memory can incorporate either new external information or a novel internal emotional state following a labile state induced by retrieval. This updating process allows editing unwanted fear memory, leading to the reduction of the fear response. Memory can be modulated by the circadian cycle. Considering that rodents are more active during the night, expressing less fearful behavior, we investigated whether fear memory can be updated when reactivated during the dark cycle. We found that rats expressed lower freezing levels during a single retrieval session in the dark cycle, but not in the test. However, three retrieval sessions in the dark cycle were able to update fear memory, reducing freezing response in the test performed in the light cycle. This effect was blocked when the glucocorticoid synthesis inhibitor metyrapone was administered before retrieval. This approach opens new avenues to explore interventions that consider the circadian cycle in the treatment of fear memories based on non-pharmacological interventions. [ABSTRACT FROM AUTHOR]