Behavioral and neurochemical effects of sodium butyrate in an animal model of mania

Abstract

The present study investigated the effect of the histone deacetylase inhibitor, sodium butyrate (SB), on locomotor behavior and on mitochondrial respiratory-chain complexes activity in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first treated with d-AMPH or saline (Sal) for 14 days. Thereafter, between days 8 and 14, rats were administered SB or Sal. In the prevention treatment, rats were treated with SB or Sal for 14 days and received d-AMPH or Sal between days 8 and 14. The d-AMPH treatment increased locomotor behavior in Sal-treated rats under reversion and prevention treatment, and SB reversed and prevented d-AMPH-related hyperactivity. Moreover, d-AMPH decreased the activity of mitochondrial respiratory-chain complexes in Sal-treated rats in the prefrontal cortex, hippocampus, striatum, and amygdala in both experiments, and SB was able to reverse and prevent this impairment. The present study suggests that the mechanism of action of SB involves induction of mitochondrial function in parallel with behavioral changes, reinforcing the need for more studies on histone deacetylase inhibitors as a possible target for new medications for bipolar disorder treatment.

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

“…38 Therefore, the finding that AMPH-induced hyperlocomotion is partially blocked by SB treatment, as well as by Li and VPT treatment, suggests that SB may have mood-stabilizing properties. 18,29 Based on this pre-established relevance of the AMPH treatment as a valid animal model of mania, we are able to suggest that the results found in our experiments can be of relevance for human patients with BD. Nevertheless, clear extrapolations to the human condition regarding the doses of the tested drugs are less likely to be made, mostly due to differences in the metabolism of rats and humans and, therefore, in the kinetics of the drugs.…”

“…11,15 SB has been shown to exhibit antidepressant properties 16,17 and can increase BDNF levels in vitro. 11 Moreover, it has recently been shown that SB reverses and prevents D-amphetamine (AMPH)-induced hyperactivity in an animal model of mania, 18 but the extent to which it is associated with HDAC activity requires further research.…”

Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats

“…In the present study, as well as Li and VPA, SB reversed the ouabaininduced hyperactivity in rats. Indeed, in recent studies from our laboratory research it was reported that SB treatment prevented and reversed the manic-like behaviors induced by ouabain and Damphetamine (Arent et al, 2011;Moretti et al, 2011;Resende et al, 2013;Stertz et al, 2014;Valvassori et al, 2013;Steckert et al, 2013).…”

Contributions of animal models to the study of mood disorders

“…In addition, SB protected against d-AMPHinduced mitochondrial complex damage and oxidative stress in the brains of rats. 132,133 Oxidative stress is an important marker present in BD and, interestingly, appears to be associated with BDNF. There is evidence showing that oxidative stress may be increased in conditions where BDNF is described to be decreased in BD.…”