Myricetin Inhibited Fear and Anxiety-Like Behaviors by HPA Axis Regulation and Activation of the BDNF-ERK Signaling Pathway in Posttraumatic Stress Disorder Rats

Abstract

Posttraumatic stress disorder (PTSD) is a stress-related psychiatric or mental disorder characterized by experiencing a traumatic stress. The cause of such PTSD is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and imbalance of monoamines. Myricetin (MYR) is a common natural flavonoid that has various pharmacological activities. We investigated the effects of MYR on fear, depression, and anxiety following monoamine imbalance and hyperactivation of HPA axis in rats exposed to a single prolonged stress (SPS). Male rats were dosed with MYR (10 and 20 mg/kg, i.p.) once daily for 14 days after exposure to SPS. Administration of MYR reduced freezing responses to extinction recall, depression, and anxiety-like behaviors and decreased increase of plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of MYR restored decreased serotonin and increased norepinephrine in the fear circuit regions, medial prefrontal cortex, and hippocampus. It also increased the reduction in the brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B mRNA expression and the ratio of p-ERK/extracellular signal-regulated kinase (ERK) in the hippocampus. Thus, MYR exerted antidepressant and anxiolytic effects by regulation of HPA axis and activation of the BDNF-ERK signaling pathway. Finally, we suggest that MYR could be a useful therapeutic agent to prevent traumatic stress such as PTSD.

Limited Cheese Intake Paradigm Replaces Patterns of Behavioral Disorders in Experimental PTSD: Focus on Resveratrol Supplementation

“…Interestingly, Freezing + rats had the lowest BDNF mRNA content among stressed rats. A considerable body of evidence suggests that freezing is associated with fear response, and certain flavonoids with pharmacological activities, such as myricetin, inhibit fear response via activation of the BDNF-ERK signaling pathway, as reported recently [ 50 ]. In general, cheese supplementation with RES further promoted the protective effects of cheese intake by inhibiting 5-HT turnover.…”

Unravelling the Link between Psychological Distress and Liver Disease: Insights from an Anxiety-like Rat Model and Metabolomics Analysis

“…The results of the behavioral test showed that the rats produced anxiety-like behaviors, but the results of the forced swimming test showed that the rats did not experience depression-like behaviors. Some studies have [22] reported that anxiety-like behaviors may lead to the dysregulation of the HPA axis. When the hypothalamus is stimulated, the pituitary gland releases ACTH, which activates the HPA axis.…”

The protective role of ginsenoside Rg3 in heart diseases and mental disorders

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