Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation

Ignácio, Zuleide M.; Réus, Gislaine Z.; Abelaira, Helena M.; Maciel, Amanda L.; de Moura, Airam B.; Matos, Danyela; Demo, Júlia P.; da Silva, Júlia B.I.; Gava, Fernanda F.; Valvassori, Samira S.; Carvalho, André F.; Quevedo, João

doi:10.1016/j.bbr.2016.11.044

Cited by 53Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation

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Ignácio, Zuleide M., Réus, Gislaine Z., Abelaira, Helena M., Maciel, Amanda L., de Moura, Airam B., Matos, Danyela, Demo, Júlia P., da Silva, Júlia B.I. +4 more·2017·Behavioural Brain Research

DOI 10.1016/j.bbr.2016.11.044

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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.

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Stressful events in childhood, adolescence, or adulthood can trigger psychiatric disorders such as depression.
“Stressful events in childhood, adolescence, or adulthood are considered villains due to their ability to trigger psychiatric disorders, such as depression or depressive-like behaviors in animals [3],[4].”
From Stress and serum cortisol levels in major depressive disorder: a cross-sectional study (2020) · cites this paper as [4]
Chronic stress throughout life involves biological changes that underlie MDD in many patients and in laboratory animals.
“Chronic stress throughout life involves several biological changes, which are underlying MDD in many patients and in laboratory animals [4],[6],[9].”
From Stress and serum cortisol levels in major depressive disorder: a cross-sectional study (2020) · cites this paper as [4]

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Authors: Ignácio, Z. M., Réus, G. Z., Abelaira, H. M., Maciel, A. L., de Moura, A. B., Matos, D., Demo, J. P., da Silva, J. B. I., Gava, F. F., Valvassori, S. S., Carvalho, A. F., & Quevedo, J.
Affiliations: Universidade Federal da Fronteira Sul (BR)
Universidade do Sul de Santa Catarina (BR)
Universidade do Extremo Sul Catarinense (BR)
Corresponding author: Réus, Gislaine Z.
ORCID: Ignácio, Zuleide M.
Réus, Gislaine Z.
Abelaira, Helena M.
Valvassori, Samira S.
Quevedo, João
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2017-03
Volume: 320
Pages: 225-232
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2016.11.044
OpenAlex: W2557438856
Cited by: 53
References: 73
Citations by year: 2026: 1 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 5 · 2014: 1
FWCI: 5.13
Type: journal article
Language: en
Open access: green
www.repositorio.ufc.br
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
Funders: Department of Psychiatry and Behavioral Sciences
McGovern Medical School
The University of Texas Health Science Center at Houston
CNPq
FAPESC
Instituto Cérebro e Mente
UNESC
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: quetiapine, maternal deprivation, major depressive disorder, DNA methylation, histone acetylation, histone deacetylase, histone acetyltransferase, DNA methyltransferases, early life stress, antidepressant-like effects, atypical antipsychotics, hippocampus, nucleus accumbens, prefrontal cortex, forced swim test
MeSH terms: Quetiapine Fumarate, DNA (Cytosine-5-)-Methyltransferase 1, Analysis of Variance, Animals, Antidepressive Agents, Anxiety Disorders, Brain, Exploratory Behavior, Female, Histone Deacetylases, Male, Maternal Deprivation, Pregnancy, Swimming, Rats, Wistar, DNA Methylation, Immobility Response, Tonic, Rats, Histone Acetyltransferases

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Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation

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