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

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-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and serum adrenocorticotropic hormone (ACTH) levels were higher in the periapical lesion group. However, rats treated with imipramine had lower IL-1 beta 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. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.