Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 256, Issue -, Pages 451-456Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2013.08.041
Keywords
Histone deacetylation; Maternal deprivation; Behavior; Depression
Categories
Funding
- 'Conselho Nacional de Desenvolvimento Cientifico e Tecnologico' (CNPq-Brazil)
- Instituto Cerebro e Mente
- UNESC
- Centro de Pesquisas, Hospital de Clinicas de Porto Alegre
- Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina (FAPESC)
- CNPq (Brazil)
- CAPES studentship
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Studies indicate that histone deacetylation is important for long term changes related to stress and antidepressant treatment. The present study aimed to evaluate the effects of the classic antidepressant imipramine, and of an antagonist of the N-methyl-D-asparte (NMDA) receptor, ketamine, on behavior and histone deacetylase (HDAC) activity in the brains of maternally deprived adult rats. To this aim, deprived and non-deprived (control) male Wistar rats were divided into the following groups: non-deprived + saline; non-deprived + imipramine (30 mg/kg); non-deprived + ketamine (15 mg/kg); deprived + saline; deprived + imipramine (30 mg/kg); and deprived + ketamine (15 mg/kg). The drugs were administrated once a day for 14 days during their adult phase. Their behavior were then assessed using the forced swimming and open field tests. In addition, the HDAC activity was evaluated in the prefrontal cortex, hippocampus, amygdala and nucleus accumbens using the kit ELISA-sandwich test. In deprived rats treated with saline, we observed an increase in the immobility time, but treatments with imipramine and ketamine were able to reverse this alteration, decreasing the immobility time. Also, there was a decrease on number of crossings with imipramine treatment in non-deprived rats, and an increase on number of crossings with ketamine treatment in deprived rats. The HDAC activity did not alter in the prefrontal cortex, hippocampus and amygdala by deprivation or via treatment with imipramine or ketamine. However, in the nucleus accumbens we observed an increase of HDAC activity in the deprived rats, and interestingly, imipramine and ketamine treatments were able to decrease HDAC activity in this brain area. These findings provide a novel insight into the epigenetic regulation of histone deacetylase in the nucleus accumbens caused by imipramine and ketamine, and indicate that molecular events are necessary to reverse specific stress-induced behavior. (C) 2013 Elsevier B.V. All rights reserved.
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