Research reportLemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice
Introduction
Pure fragrance compounds and essential oils have various effects on human and other mammalian species when inhaled or ingested, and many studies of these compounds and oils have been conducted. Some of those effects, such as the control of emotion and mood, (e.g. sedative [4], [5], [29], anxiolytic [6], [9], [11], [12], [29], antidepressant [26], [27], hypnotic [11], [36], [38], alert [11], [38]), antispasmodic [6], control of the autonomic nervous system activity [20], [35] and endocrine system [7], [30], strengthening of the immune system by stimulating the production of white blood cells [16], pain mitigation [7], anti-tumor [17], increase in lipolysis [31] etc., has been documented. Among the properties of pure fragrance compounds and essential oils, the emotional and behavioral modulations, although there are many anecdotal or empirically speculated efficacious effects, is often difficult to examine and demonstrate in a scientifically controlled conditions. Furthermore, the mechanisms of the effects of each fragrance compound or essential oil have not yet been made clear and seem to differ for each fragrance.
Some studies have suggested that essential oils affect the modulation of the central neurotransmitter system. Linalool, a major component of lavender oil, is reported to have an effect on glutamate receptors in vitro [15]. Pinene, which is one of the components of lemon oil, and lavender, hinokitiol, eugenol, citronellol, and citronellal are reported to potentiate the responses in the presence of GABA at low concentrations and inhibit the responses in the presence of GABA at high concentrations in vitro [1]. Hypericum perforatum L (St. John's wort) is supposed to inhibit the synaptosomal uptake of 5-HT in rats [19], and therefore the 5-HT concentration of basal nuclei may increase. In addition, H. perforatum L is also reported to increase extracellular dopamine levels in the rat prefrontal cortex [40].
Among the many effects of essential oil, anxiolytic and antidepressant effects are very helpful for psychiatry and psychopharmacology, since combining the medicine and essential oil can reduce the dose of those medicines and essential oil may help prevent the side effects of the anxiolytic and antidepressant medicines. All clinically available anxiolytics and antidepressants have limited clinical efficacy because of their adverse side effects, such as the amnestic effect of benzodiazepine.
In the present study, we examined the effects of inhaling lavender, rose and lemon oil vapor on mice in behavioral analyses, using the elevated plus-maze task (EPM), the open field task (OFT) and the forced swimming task (FST). Furthermore, we investigated which neurotransmitter activity was related to the anti-stress effect, by using agonists or antagonists to the benzodiazepine (BZP), 5-HT, DA and adrenaline receptors in behavioral tasks, and measured their metabolic turnovers in the prefrontal cortex, the hippocampus, and the striatum by HPLC.
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Animals
ICR strain mice were obtained from Tokyo Laboratory Animal Co., Ltd. (Tokyo, Japan) at 5 weeks old and used in all experiments after an adaptation period of 1 week. Male mice were used, because female rats showed a reduced aversion to the open arms compared to male rats in the EPM [22] and we observed similar results in mice. The mice were maintained at a controlled temperature (22 ± 2 °C) and on a regular light/dark cycle (7:00–19:00 h, light), and all animals had free access to food and water.
Behavioral changes by inhalation of essential oils
Total numbers of entries into the open and closed arms in the EPM were not significantly changed by inhalation of ethanol, lavender, rose, or lemon oil. On the other hand, the percentage of entries into the open arms was significantly increased in the lemon oil-treated mice (F(2, 30) = 18.29; P < 0.0001) (Fig. 1A-b). The time spent on the open arms was also significantly increased in the lemon oil-treated mice (F(2, 30) = 8.024; P = 0.0018) (Fig. 1A-c).
An antidepressant effect of lemon oil was more
Discussion
The present study shows that the inhalation of lemon oil vapor induced anxiolytic and antidepressant-like effects in the EPM and FST. Furthermore, significantly reduced locomotor activity and rearing behavior in the OFT were observed after 90 min of lemon oil vapor inhalation in male mice. There are many reports showing the anxiolytic [6], sedative [14], antispasmodic [39], and antidepressant [26] effects of lemon, lemon odor, or limonene in mice or rats. Limonene is one of the major components
Acknowledgement
We thank Soda Aromatic Co., Ltd. (Tokyo, Japan) for their kind provision of essential oils.
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