Gamma oryzanol impairs alcohol-induced anxiety-like behavior in mice via upregulation of central monoamines associated with Bdnf and Il-1β signaling

Abstract

Adolescent alcohol exposure may increase anxiety-like behaviors by altering central monoaminergic functions and other important neuronal pathways. the present study was designed to investigate the anxiolytic effect of 0.5% γ-oryzanol (GORZ) and its neurochemical and molecular mechanisms under chronic 10% ethanol consumption. Five-week-old ICR male mice received either control (14% casein, AIN 93 M) or GORZ (14% casein, AIN 93 M + 0.5% GORZ) diets in this study. We showed that GORZ could potentially attenuate alcohol-induced anxiety-like behaviors by significantly improving the main behavioral parameters measured by the elevated plus maze test. Moreover, GORZ treatment significantly restored the alcohol-induced downregulation of 5-hydroxytryptophan and 5-hydroxyindole acetic acid in the hippocampus and improved homovanillic acid levels in the cerebral cortex. Furthermore, a recovery increase in the level of 3-methoxy-4-hydroxyphenylglycol both in the hippocampus and cerebral cortex supported the anxiolytic effect of GORZ. The significant elevation and reduction in the hippocampus of relative mRnA levels of brain-derived neurotrophic factor and interleukin 1β, respectively, also showed the neuroprotective role of GORZ in ethanol-induced anxiety. Altogether, these results suggest that 0.5% GORZ is a promising neuroprotective drug candidate with potential anxiolytic, neurogenic, and anti-neuroinflammatory properties for treating adolescent alcohol exposure. The high prevalence of alcohol exposure among adolescents is an important issue for public health 1-3 worldwide. Chronic ethanol consumption during adolescence may alter the risk/reward assessment and damage the developing brain, leading to an increase in impulsivity 4. Furthermore, underage drinking may also increase major depression risk and anxiety disorders 5,6 later in life. In addition, central nervous monoaminergic functions are altered after adolescent ethanol exposure 7-10 and may lead to neurological changes that reduce a person's normal fear of the consequences of their actions, and contribute to risk-taking or violent behaviors. The brain is more vulnerable to alcohol during growth and development, and many studies consistently show that teens with drinking alcohol are more likely to experience alcohol-related health problems, such as obesity, diabetes, liver and heart diseases, dementia and some forms of cancer, later in life than teens who abstain. The most commonly used medicines for patients with mood and anxiety disorders exert their effects by modifying monoaminergic neurotransmission. In particular, selective serotonin reuptake inhibitors (SSRIs) target the serotonergic system and block the reuptake of serotonin from the synaptic cleft by inhibiting the serotonin transporter and enhancing the amount of free serotonin available. Notably, there is molecular, physiological, and clinical evidence suggesting that the serotonergic system plays pivotal role in the neural circuitry of mood and anxiety disorders 11-13. The functional and structural chang...

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