title: Histone deacetylase activity and brain-derived  neurotrophic factor (BDNF) levels in a pharmacological  model of mania.
abstract: OBJECTIVE
  In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples.
  
  
  METHODS
  We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma.
  
  
  RESULTS
  AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels.
  
  
  CONCLUSIONS
  Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity.
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.forename: Gabriel Rodrigo
authors.initials: GR
authors.lastname: Fries
authors.forename: Bianca Wollenhaupt de
authors.initials: BW
authors.lastname: Aguiar
authors.forename: Bianca
authors.initials: B
authors.lastname: Pfaffenseller
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Carolina
authors.initials: C
authors.lastname: Gubert
authors.forename: Camila L
authors.initials: CL
authors.lastname: Ferreira
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Keila M
authors.initials: KM
authors.lastname: Ceresér
authors.forename: Márcia
authors.initials: M
authors.lastname: Kauer-Sant'Anna
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis* / Q000187:drug effects; D020148:Butyric Acid / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000032:analysis* / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D018765:Dopamine Uptake Inhibitors; D020148:Butyric Acid; D014635:Valproic Acid; D008094:Lithium; D006655:Histone Deacetylases; D003913:Dextroamphetamine