title: 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.
authors.affiliation: Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Camila O
authors.initials: CO
authors.lastname: Arent
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Gabriel R
authors.initials: GR
authors.lastname: Fries
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.forename: Camila L
authors.initials: CL
authors.lastname: Ferreira
authors.forename: Jéssica
authors.initials: J
authors.lastname: Lopes-Borges
authors.forename: Edemilson
authors.initials: E
authors.lastname: Mariot
authors.forename: Roger B
authors.initials: RB
authors.lastname: Varela
authors.forename: Felipe
authors.initials: F
authors.lastname: Ornell
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D009420:Nervous System / Q000033:anatomy & histology* / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid