Sodium butyrate has an antimanic effect and protects the brain against oxidative stress in an animal model of mania induced by ouabain

• Butyrate reverses the hyperactivity induced by ouabain, indicating an antimanic effect.
• Ouabain increased TBARS and carbonyl content in frontal cortex and hippocampus of rats.
• Butyrate treatment reversed the lipid and protein peroxidation in both cerebral areas.
• Ouabain increased antioxidant enzymes activity in both cerebral areas of rats.
• Butyrate treatment reverses ouabain-induced catalase alteration in brains of rats.

Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidence indicates that epigenetic regulations have been implicated in the pathophysiology of mood disorders. Considering these evidences, the present study aimed to investigate the effects of sodium butyrate (SB), a histone deacetylase (HDAC)inhibitor, on manic-like behavior and oxidative stress parameters (TBARS and protein carbonyl content and SOD and CAT activities) in frontal cortex and hippocampus of rats subjected to the animal model of mania induced by intracerebroventricular (ICV) ouabain administration.The results showed that SB reversed ouabain-induced hyperactivity, which represents a manic-like behavior in rats. In addition, the ouabain ICV administration induced oxidative damage to lipid and protein and alters antioxidant enzymes activity in all brain structures analyzed. The treatment with SB was able to reversesboth behavioral and oxidative stress parameters alteration induced by ouabain.In conclusion, we suggest that SB can be considered a potential new mood stabilizer by acts on manic-like behavior and regulatesthe antioxidant enzyme activities, protecting the brain against oxidative damage.