Neuroanatomical Profile of Antimaniac Effects of Histone Deacetylases Inhibitors

Abstract

An increasing number of studies have evaluated the potential therapeutic relevance of histone deacetylases (HDAC) inhibitors in mood disorder including bipolar disorder (BD). It has been suggested that the anterior limbic, which controls impulsivity and psychosis, is dysfunctional in BD. The present studies aims to evaluate the effects of microinjection of HDAC inhibitors in the ventricle, amygdala, striatum, prefrontal, and hippocampus on m-amphetamine-induced manic-like behavior in rats. Rats were given a single intracerebral (in the ventricle, amygdala, striatum, prefrontal, or hippocampus) injection of artificial cerebrospinal fluid, sodium butyrate (SB), or valproate (VPA) followed by an intraperitoneal injection of saline or m-AMPH 2 h before the open-field task. The activity of HDAC was evaluated in amygdala, striatum, prefrontal, and hippocampus of animals. The microinjection of SB and VPA in the ventricle, amygdala, striatum, and prefrontal, but not in hippocampus blocked the hyperactivity induced by m-AMPH. In addition, SB and VPA inhibited the HDAC activity; however, this effect varied depending on the experimental procedure and the brain structure evaluated. Our results suggest that the antimanic effects of SB and VPA, HDAC inhibitors, are related to the amygdala, striatum, and prefrontal, but not the hippocampus. More studies are needed to clarify the therapeutic effects of the HDAC inhibitor in BD and thereby develop new drugs.