Increase in histone acetylation rescues a weak remote fear memory in rats

Abstract

There is a growing body of evidence of memory-enhancing effects of histone deacetylase (HDAC) inhibitors in different species and models. Less clearly is understood whether the increased histone acetylation is able to facilitate the remote fear memory. Thus, the aim of the current study was to examine the ability of HDAC inhibitor sodium butyrate (SB) to ameliorate weakening of the remote fear memory in rats. To assess the ability of HDAC inhibitor SB to improve remote fear memory we compared the performance of two laboratory strains of rats, Wistar and Long-Evans, in context fear conditioning task six months after training before and after the SB administration. We found that the rats showed a strong fear response to the context 24 h after the end of conditioned fear training, full absence of fear after 6 months, and high fear response after the SB administration without additional learning. In control experiments, we found that time-dependent decrease in conditioned fear response to the context was similar in rats under vehicle administration. Moreover, the data obtained showed that both rats’ strains showed a similar decrease in freezing response over time, and HDAC inhibition improved the weak remote fear memory in both of them. In addition, the decrease in freezing and memory reinstatement by males matched completely to the female rats’ performance. These results indicate that HDAC inhibition appears to have the same “rescue” effects on remote fear memory reinstatement regardless of the strain and gender of rats.