Imipramine treatment reverses depressive- and anxiety-like behaviors, normalize adrenocorticotropic hormone, and reduces interleukin-1β in the brain of rats subjected to experimental periapical lesion

Lutiana R. Simões, Soraia Netto, Jaqueline S. Generoso, Renan A. Ceretta, Rodrigo F. Valim, Diogo Dominguini, Monique Michels, Gislaine Z. Réus, Samira S. Valvassori, Felipe Dal-Pizzol, Tatiana Barichello

Research output: Contribution to journalArticle

Abstract

Background: A periodontal lesion is a consequence of chronic inflammatory processes, itself triggered by a bacterial infection of the pulpal and endodontic microenvironment. Evidence suggests that periodontal lesion induction could alter inflammatory cytokines leading to behavior changes. These effects in the context of anxiety and depressive behavior have been not full investigated. We aimed to observe anxiety- and depressive-like behavioral in rodent subjected to periapical dental lesions. Methods: Pro-inflammatory cytokines levels also were investigated in the frontal cortex and hippocampus. Parameters related to hypothalamic–pituitary–adrenal (HPA) axis activation also were evaluated. Wistar rats were divided in groups: control/saline; control/imipramine; periapical lesion/saline; and periapical lesion/imipramine. Three weeks after induction of the periapical dental lesion, they were subjected to behavioral tests. Results: In the periapical lesion group was demonstrated anhedonic behavior and depressive-like behavior. In the elevated plus-maze test the periapical lesion group had an increase in the number of entries and spent more time in the closed arms. Imipramine treatment was able to reverse depressive- and anxiety-like behaviors. In the hippocampus and frontal cortex tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and serum adrenocorticotropic hormone (ACTH) levels were higher in the periapical lesion group. However, rats treated with imipramine had lower IL-1β and ACTH levels. Conclusions: Our results revealed depressive- and anxiety-like behaviors following induction of a specific dental lesion. These effects could be associated to higher levels of brain pro-inflammatory cytokines and HPA axis changes. Antidepressants treatments could be an alternative to treat comorbidities associated to periodontal lesions.

LanguageEnglish
Pages24-31
Number of pages8
JournalPharmacological Reports
Volume71
Issue number1
DOIs
StatePublished - Feb 1 2019

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Imipramine
Major Depressive Disorder
Interleukin-1beta
Adrenocorticotropic Hormone
Anxiety
Inflammation
Brain
Tooth
Frontal Lobe
Cytokines
Hippocampus
Endodontics
Bacterial Infections
Antidepressive Agents
Comorbidity
Wistar Rats
Rodentia
Interleukin-6
Tumor Necrosis Factor-alpha
Pharmacology

Keywords

  • Anxiety
  • Imipramine
  • Inflammation
  • Major depressive disorder
  • Periodontal lesion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Imipramine treatment reverses depressive- and anxiety-like behaviors, normalize adrenocorticotropic hormone, and reduces interleukin-1β in the brain of rats subjected to experimental periapical lesion. / Simões, Lutiana R.; Netto, Soraia; Generoso, Jaqueline S.; Ceretta, Renan A.; Valim, Rodrigo F.; Dominguini, Diogo; Michels, Monique; Réus, Gislaine Z.; Valvassori, Samira S.; Dal-Pizzol, Felipe; Barichello, Tatiana.

In: Pharmacological Reports, Vol. 71, No. 1, 01.02.2019, p. 24-31.

Research output: Contribution to journalArticle

Simões, LR, Netto, S, Generoso, JS, Ceretta, RA, Valim, RF, Dominguini, D, Michels, M, Réus, GZ, Valvassori, SS, Dal-Pizzol, F & Barichello, T 2019, 'Imipramine treatment reverses depressive- and anxiety-like behaviors, normalize adrenocorticotropic hormone, and reduces interleukin-1β in the brain of rats subjected to experimental periapical lesion' Pharmacological Reports, vol. 71, no. 1, pp. 24-31. https://doi.org/10.1016/j.pharep.2018.08.003
Simões, Lutiana R. ; Netto, Soraia ; Generoso, Jaqueline S. ; Ceretta, Renan A. ; Valim, Rodrigo F. ; Dominguini, Diogo ; Michels, Monique ; Réus, Gislaine Z. ; Valvassori, Samira S. ; Dal-Pizzol, Felipe ; Barichello, Tatiana. / Imipramine treatment reverses depressive- and anxiety-like behaviors, normalize adrenocorticotropic hormone, and reduces interleukin-1β in the brain of rats subjected to experimental periapical lesion. In: Pharmacological Reports. 2019 ; Vol. 71, No. 1. pp. 24-31.
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abstract = "Background: A periodontal lesion is a consequence of chronic inflammatory processes, itself triggered by a bacterial infection of the pulpal and endodontic microenvironment. Evidence suggests that periodontal lesion induction could alter inflammatory cytokines leading to behavior changes. These effects in the context of anxiety and depressive behavior have been not full investigated. We aimed to observe anxiety- and depressive-like behavioral in rodent subjected to periapical dental lesions. Methods: Pro-inflammatory cytokines levels also were investigated in the frontal cortex and hippocampus. Parameters related to hypothalamic–pituitary–adrenal (HPA) axis activation also were evaluated. Wistar rats were divided in groups: control/saline; control/imipramine; periapical lesion/saline; and periapical lesion/imipramine. Three weeks after induction of the periapical dental lesion, they were subjected to behavioral tests. Results: In the periapical lesion group was demonstrated anhedonic behavior and depressive-like behavior. In the elevated plus-maze test the periapical lesion group had an increase in the number of entries and spent more time in the closed arms. Imipramine treatment was able to reverse depressive- and anxiety-like behaviors. In the hippocampus and frontal cortex tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and serum adrenocorticotropic hormone (ACTH) levels were higher in the periapical lesion group. However, rats treated with imipramine had lower IL-1β and ACTH levels. Conclusions: Our results revealed depressive- and anxiety-like behaviors following induction of a specific dental lesion. These effects could be associated to higher levels of brain pro-inflammatory cytokines and HPA axis changes. Antidepressants treatments could be an alternative to treat comorbidities associated to periodontal lesions.",
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AU - Netto, Soraia

AU - Generoso, Jaqueline S.

AU - Ceretta, Renan A.

AU - Valim, Rodrigo F.

AU - Dominguini, Diogo

AU - Michels, Monique

AU - Réus, Gislaine Z.

AU - Valvassori, Samira S.

AU - Dal-Pizzol, Felipe

AU - Barichello, Tatiana

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