Serotonergically dependent antidepressant-like activity on behavior and stress axis responsivity of acacetin. (August 2019)

• Record Type: Journal Article
• Authors: Xiao, Wen-Ze; Zhou, Wen-Hua; Ma, Qing; Cui, Wu-Geng; Mei, Qi-Yong; Zhao, Xin
• Is Part Of: Pharmacological research. Volume 146(2019)
• Publication Date: 2019-08
• Subjects: Acacetin -- Antidepressant-like effect -- Stress -- Serotonergic system; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.104310
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Acacetin, a natural flavonoid, possesses broad spectrum of pharmacological and biochemical activities, such as neuroprotection, antinociception and inhibition of monoamine oxidase. The current work aimed to investigate the antidepressant-like activity of acacetin in mice and explore the underlying mechanism(s). Chronic, but not acute, acacetin treatment (5, 15 or 45 mg/kg, p.o., once per day for three weeks) exerted in mice dose-dependently antidepressant-like activity, assessed by forced swim test (FST) and tail suspension test (TST). Although acacetin-treated mice showed normal circadian hypothalamo-pituitary-adrenal (HPA) axis activity, their endocrine responsivity to both acute restraint stress and intracerebroventricular injection of corticotropin-releasing factor (CRF) was buffered. The acacetin-triggered antidepressant-like activities are serotonergically dependent, since its impacts on behavior and stress responsivity were totally abolished by chemical depletion of brain serotonin by PCPA. Consistently, acacetin-treated mice showed escalated levels of brain monoamines especially serotonin and depressed activity of monoamine oxidase. Moreover, the acacetin-evoked anti-depression was preferentially counteracted by co-administration of 5-HT1A receptor antagonist WAY-100635, but potentiated by 5-HT1A receptor agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine, suggesting a pivotal engagement of 5-HT1A related serotonergic system. In vitro, acacetin (1–100 nM) increased the Emax of 8-OH-DPAT. Collectively, these findings confirm that chronic acatetin administration to mice engenders antidepressant-like efficacy on both behavior and stress axis responsivity, with serotonergic system that preferentially couples with 5-HT1A receptors being critically involved.