Myricitrin exhibits antidepressant-like effects and reduces IL-6 hippocampal levels in the chronic mild stress model

• Published in: Behavioural brain research 2022-07, Vol.429, p.113905-113905, Article 113905
• Main Authors: Pereira, Marcela, Siba, Isadora P., Acco, Alexandra, Correia, Diego, Lapa, Fernanda R., Santos, Adair R.S., Ruani, Ana P., Pizzolatti, Moacir G., Andreatini, Roberto
• Format: Article
• Language: English
• Subjects: Anhedonia; Antidepressant; Cytokines; Forced swim; Medicin och hälsovetenskap; Mice; Tail suspension
• ISSN: 0166-4328; 1872-7549; 1872-7549
• DOI: 10.1016/j.bbr.2022.113905

The flavonoid myricitrin showed an antidepressant-like effect in the tail suspension test and increased hippocampal neurogenesis, as well as demonstrating anti-inflammatory effects. Interestingly, inflammation has been linked to depression, and anti-inflammatory drugs showed promising results as antidepressant-like drugs. Thus, the present study evaluated the effects of myricitrin in the chronic mild stress (CMS) model, a translational and valid animal model of depression, using the mini-experiment design to improve the reproducibility of the findings. The sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were the readouts of depressive-like phenotypes induced by CMS. Relative adrenal weight was employed as an index of the hypothalamus–pituitary–adrenal (HPA) axis activation. Interleukin (IL)−6 and tumor necrosis factor (TNF)-alpha levels were measured in the hippocampus. Myricitrin (10 mg/kg, intraperitoneally, for 14 days) reversed depressive-like behaviors induced by CMS (increased immobility in the FST, the TST and anhedonia), as well as decreased adrenal hypertrophy and hippocampal levels of IL-6 in stressed mice. Similar results were observed by imipramine (20 mg/kg, intraperitoneally, for 14 days), a serotonin and norepinephrine reuptake inhibitor (positive control). A significant correlation was observed between immobility time in the TST, and hippocampal IL-6 levels. Hippocampal TNF-α levels were not affected by CMS or drug treatment. In conclusion, myricitrin exhibited an antidepressant-like profile in CMS, and this effect may be associated with its anti-inflammatory activity. •Myricitrin had antidepressant-like effects in the chronic mild stress (CMS) model.•Myricitrin blocked hippocampal level increase of interleukine-6 induced by CMS.•Myricitrin reduced CMS-induced Hypothalamic-Pituitary-Adrenal axis activation.•Immobility time in the tail suspension test and IL-6 showed a positive correlation.•Thus, myricitrin shows antidepressant-like effects in the CMS model.