Sodium butyrate as a selective cognitive enhancer for weak or impaired memory

Several recent studies showed that memory can be modulated by manipulating chromatin modifications using histone deacetylase (HDAC) inhibitors during memory formation, consolidation, and reconsolidation. We used a context fear conditioning paradigm with minimal non-painful current as a reinforcement, what elicited alertness to the context and freezing during tests in rats. Such paradigm resulted in a relatively weak memory in significant part of the rats. Here, we demonstrate that intraperitoneal administration of the HDAC inhibitor sodium butyrate immediately following memory reactivation, produced memory enhancement in rats with weak memory, however, not in rats with strong memory. Additionally, we investigated the ability of the HDAC inhibitor sodium butyrate to restore the contextual memory impaired due to the blockade of protein synthesis during memory reactivation. The results obtained evidence that the HDAC inhibitor sodium butyrate reinstated the impaired contextual memory. This enhancement effect is consistent with other studies demonstrating a role for HDAC inhibitors in the facilitation of contextual fear.