Abstract Rationale Fear memories are essential for survival, but their inappropriate expression can contribute to anxiety disorders, phobias, and post-traumatic stress disorders that can present differently between the sexes. Memory reconsolidation is a process through which previously stored memories can be modified upon reactivation. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway regulates neuronal gene transcription and is involved in synaptic plasticity and memory formation. Evidence suggests possible sex differences in the neurobiological mechanisms underlying fear responses and memory processes. However, its involvement in the reconsolidation of contextual fear conditioning (CFC) memory in male and female rats remains unclear. Objective To investigate the involvement of the MAPK/ERK pathway in the CA1 region of the dorsal hippocampus during CFC memory reconsolidation in male and female Wistar rats. Methods The role of the MAPK/ERK pathway was evaluated by infusing the selective inhibitor U0126 (0.04 µg/side) into the hippocampus at different time points after the reactivation session. Results The results demonstrated that, in both male and female rats, the inhibition of the MAPK/ERK pathway in the CA1 region impaired the CFC memory reconsolidation when administered immediately and 3 h after the reactivation session. However, this effect was not observed when administered 6 h later. Conclusions These findings indicate the involvement of the MAPK/ERK signaling pathway in the CA1 region of the hippocampus in the reconsolidation of contextual fear conditioning memory in male and female rats and provide new insights into the molecular mechanisms underlying memory reconsolidation, highlighting a common molecular mechanism across sexes.
Ludwig et al. (Thu,) studied this question.