Novelty exposure hinders aversive memory generalization and depends on hippocampal protein synthesis

Fear generalization is defined as the transferring of fear experienced during a traumatic event to safe conditions resembling or not the traumatic event. It has been related to several psychological disorders. Here we set out to determine whether novelty exposure can be effective to avoid fear generalization. We evaluated the effect of a novelty exposure on fear memory generalization using an aversive memory task, the inhibitory avoidance (IA). Male Wistar rats were trained in IA (day 1) and 24 h after (day 2) they were exposed to a new context similar to the original (modified IA - MIA), with some rats being exposed to a novelty just before the exposure to the MIA, while others were not (controls). On day 3, retention tests for IA and MIA contexts were performed. The control rats generalized the memory, expressing aversive behavioral in both contexts whereas rats exposed to novelty only expressed aversion on IA. Furthermore, both anisomycin, an inhibitor of ribosomal protein synthesis, and rapamycin, an inhibitor of mTOR-mediated protein synthesis, injected in the CA1 region of dorsal hippocampus blocked the novelty effect, promoting memory generalization. We conclude that novelty exposure hinders aversive memory generalization depending on hippocampal protein synthesis.