Phospho-acetylation of histone H3 in the amygdala after acute lithium chloride.

Acute injection of a high dose of lithium chloride (LiCl) increases c-Fos expression in the central nucleus of the amygdala (CeA). We investigated if LiCl-induced c-Fos expression in the CeA is correlated with histone acetylation and phospho-acetylation. Chromatin modifications such as acetylation and phosphorylation are necessary for optimal gene expression, and gene expression may be increased by inhibiting the activity of histone deacetylases. LiCl (0.15 M, 12 ml/kg, i.p.) highly increased the levels of acetylation and phospho-acetylation of histone H3 in the CeA. The time course of these increases closely corresponded to and preceded the time course of c-Fos induction. Moreover, LiCl-induced c-Fos was co-localized with phospho-acetylated histone H3 in a majority of c-Fos-positive cells in the CeA. Systemic administration of a histone deacetylase inhibitor, sodium butyrate (NaB; 0.3 M, 0.4 g/kg, i.p.), significantly increased the levels of LiCl-induced c-Fos and phospho-acetylated histone H3 in the CeA. NaB also enhanced conditioned taste aversion learning induced by pairing saccharin consumption with LiCl injection, by making the conditioned taste aversion more resistant to extinction. These results suggest that LiCl-induced c-Fos expression may be regulated by modification of histone H3, especially phospho-acetylation, in the CeA. Furthermore, the level of phospho-acetylation of histone H3, c-Fos induction, and amygdalar-dependent taste aversion learning is constrained by endogenous histone deacetylase activity.