title: Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation.
abstract: Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD.
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil; Laboratory of Physiology, Pharmacology and Psychopathology, Campus Chapecó, Federal University of South Frontier, Chapecó, Santa Catarina, Brazil.
authors.forename: Zuleide M
authors.initials: ZM
authors.lastname: Ignácio
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil. Electronic address: gislainezilli@hotmail.com.
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Abelaira
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Maciel
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Airam B
authors.initials: AB
authors.lastname: de Moura
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Danyela
authors.initials: D
authors.lastname: Matos
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Júlia P
authors.initials: JP
authors.lastname: Demo
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Júlia B I
authors.initials: JB
authors.lastname: da Silva
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil; Laboratory of Neural Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Gava
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil; Laboratory of Neural Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil; Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Neuroscience Graduate Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000209:etiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D008426:Maternal Deprivation; D011247:Pregnancy; D000069348:Quetiapine Fumarate / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D000069348:Quetiapine Fumarate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619382:Dnmt1 protein, rat; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases
keywords: Antidepressant; Epigenetic; Major depressive disorder; Maternal deprivation; Quetiapine