ReferenceID 3891
Serotonergically dependent antidepressant-like activity on behavior and stress axis responsivity of acacetin
Pharmacol Res
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 t
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Record Fields
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- Reference Id
- 3891
- Evidence Id
- 20481
- Core Evidence Id
- 20481
- Source Reference Id
- 1069
- Herb2 Reference Id
- HBREF001801
- Subject Paper Key
- HBIN014294_31229563
- Pubmed Id
- 31229563
- Doi
- 10.1016/j.phrs.2019.104310
- Paper Title
- Serotonergically dependent antidepressant-like activity on behavior and stress axis responsivity of acacetin
- Paper 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.
- Journal
- Pharmacol Res
- Publish Year
- 2019
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Depression; Hypothalamo-pituitary-adrenal (hpa) Axis
- Paper Title Cn
- Paper Title En
- Serotonergically dependent antidepressant-like activity on behavior and stress axis responsivity of acacetin
- Bilingual Status
- semi_complete