Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms

The fate of memories depends mainly on two opposing forces: the mechanisms required for the storage and maintenance of memory and the mechanisms underlying forgetting, being the latter much less understood. Here, we show the effect of inhibiting the small Rho GTPase Rac1 on the fate of inhibitory avoidance memory in male rats. The immediate post-training micro-infusion of the specific Rac1 inhibitor NSC23766 (150 ng/0.5 µl/ side) into the ventral tegmental area (VTA) enhanced long-term memory at 1, 7, and 14 days after a single training. Additionally, an opposed effect occurred when the inhibitor was infused at 12 h after training while no effect was observed immediately after testing animals at 1 day. Control experiments ruled out the possibility that post-training memory enhancement was due to facilitation of memory formation since no effect was found when animals were tested at 1 h after acquisition and no memory enhancement was observed after the formation of a weak memory. Immediate post-training micro-infusion of Rac1 inhibitor into the dorsal hippocampus, or the amygdala did not affect memory. Our findings support the idea of a Rac1-dependent time-specific active forgetting mechanism in the VTA controlling the strength of a long-term aversive memory.