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

Sci Rep. 2020 Jun 30;10(1):10677. doi: 10.1038/s41598-020-67689-w.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / chemically induced
  • Anxiety / drug therapy*
  • Anxiety / metabolism
  • Anxiety Disorders / chemically induced
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / metabolism
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Ethanol / adverse effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Interleukin-1beta / metabolism*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred ICR
  • Neuroprotective Agents / pharmacology
  • Phenylpropionates / pharmacology*
  • Signal Transduction / drug effects
  • Transcriptional Activation / drug effects
  • Up-Regulation / drug effects*


  • Anti-Anxiety Agents
  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Interleukin-1beta
  • Neuroprotective Agents
  • Phenylpropionates
  • Ethanol
  • gamma-oryzanol