Frontiers in Pharmacology 2020
Gamma Oryzanol Alleviates High-Fat Diet-Induced Anxiety-Like Behaviors Through Downregulation of Dopamine and Inflammation in the Amygdala of Mice.
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Methods
Eight-week-old Institute of Cancer (ICR) male mice weighing 33-34 g were divided into the following groups and free-fed for 8 weeks: control (14% casein, AIN 93M); HFD; HFD + GORZ (0.5% GORZ). Body weight gain was checked weekly. The anxiolytic-like effects of GORZ were examined via open-field test (OFT) and elevated plus maze (EPM) test. Brain levels of monoamines [5-hydroxy tryptamine (5-HT), dopamine (DA), and norepinephrine (NE)] and their metabolites [5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], proinflammatory cytokines such as tumor necrosis factor-αα (Tnf-α) mRNA levels, and interleukin 1-β (Il-1β) mRNA levels in the cerebral cortex and amygdala were examined using high-performance liquid chromatography-electrochemical detection (HPLC-ECD), and real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively.Results
Mice fed a HFD for eight weeks showed anxiety-like behaviors in association with HFD-induced body weight gain. GORZ potentially blocked HFD-induced anxiety-like behaviors via significant improvement of the primary behavioral parameters in behavioral tests, with a minor reduction in HFD-induced body weight gain. Furthermore, GORZ treatment significantly downregulated HFD-induced upregulation of dopamine levels in the brain's amygdala. Significant reduction of the relative mRNA expression of Tnf-α and Il-1 β was also observed in the amygdala of HFD + GORZ mice, compared to HFD mice.Conclusions
Our findings strongly suggest that 0.5% GORZ exerts anxiolytic-like effects, possibly through downregulation of dopamine, and via expression of proinflammatory cytokines Tnf-α and Il-1 β in the case of chronic HFD exposure.