Sub-chronic effects of s-limonene on brain neurotransmitter levels and behavior of rats

J Nutr Sci Vitaminol (Tokyo). 2009 Aug;55(4):367-73. doi: 10.3177/jnsv.55.367.


The present study was designed to gain insight into the effects of s-limonene on the brain after 1-wk administration. For this purpose, neurotransmitters such as dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamic acid (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC-ECD and amino acid analyzer after 1-wk administration of s-limonene of different concentrations (0, 5, 25, 50 mg/kg). Significant changes, such as GABA, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time, basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of s-limonene was evaluated by corticosterone. Considering the increment of GABA and the changes of other neurotransmitters, anti-stress effects after 1-wk administration were observed. The experimental results showed that s-limonene could inhibit HPA activity under physical stress and this anti-stress effect of s-limonene may act through the GABA(A) receptor.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Corticosterone
  • Cyclohexenes / pharmacology*
  • Dopamine / metabolism
  • GABA Agonists / pharmacology
  • Glutamic Acid / metabolism
  • Hypothalamo-Hypophyseal System / drug effects
  • Limonene
  • Male
  • Neurotransmitter Agents / metabolism*
  • Oils, Volatile / pharmacology
  • Pituitary-Adrenal System / drug effects
  • Plant Extracts / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Stress, Physiological / drug effects*
  • Terpenes / pharmacology*
  • gamma-Aminobutyric Acid / metabolism*


  • Cyclohexenes
  • GABA Agonists
  • Neurotransmitter Agents
  • Oils, Volatile
  • Plant Extracts
  • Terpenes
  • Serotonin
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Limonene
  • Dopamine
  • Corticosterone