Sub-Chronic Effects of s-Limonene on Brain Neurotransmitter Levels and Behavior of Rats

Abstract

SummaryThe 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), ␥ -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. Key Words s -limonene, anti-stress effects, GABA, 5-HT, foot shock s -Limonene is a component of lemon essential oil. It has been reported that acute administration of slimonene at high concentration can relieve physical and psychological stress ( 1 ). There are other reports about its acute functions in modifying monoamine levels in rat brains and brain waves from human tests ( 2 ). In addition, some researchers have also demonstrated by the microdialysis method that lemon essential oil components could stimulate the release of acetylcholine when rats were facing persistent painful stimulation ( 3 ). From these reports, we thought that s -limonene showed potential to be used as a medical additive or substitute therapy in the pharmaceutical field for helping people troubled by stress. However, it is unknown what happens in the brain after chronic or sub-chronic administration of s -limonene.In this study, the effects of 1-wk administration of slimonene on neurotransmitters were determined, and the possible anti-stress effects were evaluated. The possible relationship between neurotransmitter changes and anti-stress effects was also explored. MATERIALS AND METHODS Animals.Wistar male rats (200-250 g) (Japan SLC, Inc., Shizuoka, Japan) were individually housed at 23 Ϯ 1˚C in a room with a 12-h light-dark cycle. Rats were given a commercial diet (stock diet: CE-2, CLEA Japan, Inc., Tokyo, Japan). Foodstuff and water were freely available. Rats in each group were only used once with one purpose. The experimental procedures were in accordance with the guidelines of the University of Shizuoka for the Care and Use of Laboratory Animals, based on those of the American Association for Laboratory Animal Science.Dose-dependent changes of neurotransmitters induced by 1-wk administration of s-limonene. Seventy-two rats were split randomly into 4 groups (18 rats per group) , with similar body weights among the groups. The rats were orally administered corn oil (1 mL/kg, vehicle) or s -limonene dissolved in corn oil (5, 25, or 50 mg/kg) accord...

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“…Due to the increased concentration of GABA and the changes of other neurotransmitters, an anti‐stress effect was assumed. After that, the results showed that ( S )‐limonene inhibits HPA activity under physical stress and the stress‐alleviating effect possibly acted by the GABA A receptor …”

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