The Anxiolytic-Like Effects of Protocatechuic Acid in an Animal Model of Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by impaired fear extinction, depression, and anxiety caused by dysregulation of the hypothalamic-pituitary-adrenal axis and an imbalance of monoamines. Protocatechuic acid (PCA; 3,4-dihydroxybenzoic acid), a major polyphenol metabolite, has various pharmacological effects, such as anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. In this study, the efficacy of PCA for fear extinction, antidepressant, and anxiolytic effects in PTSD-mediated psychiatric disorders, were evaluated by exposing rats to single prolonged stress (SPS). Male rats were administered PCA (100 or 200 mg/kg) once daily for 14 days after exposure to SPS. PCA significantly decreased situational fear, depressive and anxiety-like behaviors, and corticosterone levels. In addition, PCA regulated the imbalance of serotonin and norepinephrine in the fear circuit region (i.e., the medial prefrontal cortex and hippocampus [Hipp]), and suppressed the decrease in brain-derived neurotrophic factor mRNA expression in the Hipp. The results showed that PCA administration improves freezing behavior and has antidepressant and anti-anxiety effects through modulation of the serotonergic nervous system and monoamines in rats. These results indicated that PCA may be useful as a food ingredient to prevent PTSD.

Automated summary

The results of this study suggest that protocatechuic acid (PCA) can improve fear extinction, depression, and anxiety symptoms in rats by modulating the serotonergic nervous system and monoamines. This indicates that PCA may have potential in preventing post-traumatic stress disorder (PTSD).