title: Ketamine and imipramine in the nucleus accumbens regulate histone deacetylation induced by maternal deprivation and are critical for associated behaviors.
abstract: 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.
authors.affiliation: Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. Electronic address: gislainezilli@hotmail.com.
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.forename: Helena M
authors.initials: HM
authors.lastname: Abelaira
authors.forename: Maria Augusta B
authors.initials: MA
authors.lastname: dos Santos
authors.forename: Anelise S
authors.initials: AS
authors.lastname: Carlessi
authors.forename: Débora B
authors.initials: DB
authors.lastname: Tomaz
authors.forename: Morgana V
authors.initials: MV
authors.lastname: Neotti
authors.forename: João Lucas G
authors.initials: JL
authors.lastname: Liranço
authors.forename: Carolina
authors.initials: C
authors.lastname: Gubert
authors.forename: Maurício
authors.initials: M
authors.lastname: Barth
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000107:Acetylation; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008426:Maternal Deprivation; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D006657:Histones; D007649:Ketamine; D007099:Imipramine
keywords: Behavior; Depression; HDAC; Histone deacetylation; Maternal deprivation; N-methyl-d-asparte; NMDA; histone deacetylase