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

Revista Brasileira de Psiquiatria

Laura Stertz¹  Gabriel Rodrigo Fries¹  Bianca Wollenhaupt De Aguiar¹  Bianca Pfaffenseller¹  Samira S. Valvassori¹  Carolina Gubert¹  Camila L. Ferreira¹  Morgana Moretti¹  Keila M. Ceresér¹  Márcia Kauer-sant'anna¹  João Quevedo¹  Flavio Kapczinski¹ 

关键词: Bipolar disorder;    mood stabilizer;    sodium butyrate;    histone deacetylase;    BDNF;   

DOI  :  10.1590/1516-4446-2013-1094

来源: SciELO

【 摘 要 】

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. Conclusion: 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.

【 授权许可】

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