Anxiolytic effects of Lavandula angustifolia odour on the Mongolian gerbil elevated plus maze
Introduction
The cost of anxiety disorders in terms of prescription medicine in the UK is £5 billion per annum (Malizia, 2002). Aromatherapy is becoming an increasingly popular treatment option for those suffering from anxiety with the rationale that essential oils are inhaled and have a direct effect on the limbic system were anxious emotions are generated (Perry and Perry, 2006). Of the essential oils available, Lavender (Lavandula angustifolia) odour is one of the most commonly used and in keeping with this there is a large demand for lavender oil in the general population (Price and Price, 1999).
There is some evidence for the effectiveness of lavender oil in the treatment of anxiety in humans. Lehrner et al. found lavender odour to be effective in relieving anxious mood in dental patients exposed to lavender in the waiting room (Lehrner et al., 2005).
While in humans cognitive mechanisms of odour transduction may confound pharmacological effects, animal studies give some evidence for essential oils having pharmacological properties. Lavender oil exhibits spasmolytic properties on guinea pig ileum and rat uterus in vitro, which has been suggested as an explanation of its possible mechanism of action in the reported holistic relaxant effects in humans (Lis-Balchin and Hart, 1999). Lavender oil and its major component linalool have been shown to alter plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in ovariectomised rats, these hormones have a role to play in the stress response and may explain any tension relieving properties of lavender (Yamada et al., 2005). Furthermore lavender has been found to potentiate barbiturate sleeping time in the mouse, which may indicate an interaction with the GABA-A receptor (Guillemain et al., 1989). In support of this, lavender has also been found to potentiate the actions of GABA-A receptors in Xenopus oocytes (Aoshima and Hamamoto, 1999). GABA is widely known to be involved in the aetiology of anxiety, hence the short term effectiveness of diazepam, a GABA agonist, in relieving anxiety.
Lavender also shows direct behavioural effects: using an associative conditioning paradigm, injected lavender oil produced dose- dependent anti-conflict effects similar to those observed with diazepam (Umezu, 2000).
The elevated plus maze (EPM) is a commonly used non-conditioned model of anxiety for rats and mice. Non-conditioned models such as the EPM may be more ecologically valid than conditioned models because they utilise the animals’ naturally occurring anxiety-related behaviours (Flint, 2003). The EPM shows bi-directional sensitivity to anxiolytic and anxiogenic agents by providing animals with free access to anxiety-provoking and anxiety-relieving environments (Pellow et al., 1985, Hogg, 1996). At present only one study has used the EPM to test the effects of lavender; in this case it was diluted 1/60 in olive oil and fed to mice. Results showed sedative but not anxiolytic effects (Guillemain et al., 1989). In humans exposure to lavender is more often via the olfactory route, and odours are hypothesized to have a direct effect on the limbic system, via the nose and olfactory cortex. This excludes the possibility of any chemical alterations to the oils by the digestive system.
Although mice and rats have been used extensively in behavioural models of anxiety, they may not be an optimal species for generalisation to humans. Recent research has shown that the Mongolian gerbil (Meriones unguiculatus), shares greater neuro-endocrinological similarities to humans. For example, the gerbil neurokinnin receptor is more similar to the human neurokinin receptor than that of rats or mice (Varty et al., 2002a, Varty et al., 2002b, Bridges and Starkey, 2004). In the search for drugs to treat anxiety which do not have the wide ranging and debilitating side effects of the benzodiazepines, neurokinin receptors have been implicated in the aetiology of anxiety (Walsh et al., 1995, Gerlai et al., 2002). The neurokinin-1 receptor shows a different affinity for neurokinin-1 receptor ligands across species, for this reason certain agents that work in humans are less active in rats and mice. These receptors are distributed in particularly high amounts in the olfactory bulb, olfactory cortex and also limbic structures. The limbic system is where emotions such as anxiety are generated. The main ligand to bind to neurokinin-1 receptors is a peptide known as substance P. Substance P is extensively co-localised with classical neurotransmitters involved in the aetiology of anxiety such as serotonin, noradrenalin and glutamate. Neurokinin antagonists are thought to enhance 5HT and noradrenalin transmission via presynaptic mechanisms in a similar manner to anxiolytic and antidepressant drugs (Gobi and Blier, 2005).
A recent validation of the EPM for gerbils has demonstrated sensitivity to anxiolytic and anxiogenic agents, such as those which act on GABA and 5HT systems, in a similar way to rats and mice indicating that this test is suitable for use in this species (Varty et al., 2002a).
It has been suggested that any anxiety-alleviating effects caused by essential oils in humans are probably immediate but short lived (Cooke and Ernst, 2000). The aim of this study was to test the effects of continuous lavender odour exposure over 24 h and a longer term of 2 weeks on gerbil EPM behaviour.
A second study examined the effect of 30 min or 14-day i.p. diazepam administration to identify whether chronic exposure to lavender odour gave a similar behavioural fingerprint to that of diazepam.
Section snippets
Materials and methods
Male and female gerbils were randomly assigned to either a no odour control group (NO), an acute lavender odour group (a single 24 h exposure before and during testing) (AL) or a chronic odour group (24 h per day for 14 days) (CL). To assess the effects of diazepam and provide a comparison of the effects of chronic lavender odour with a known anxiolytic diazepam, a further experiment was conducted, comparing the effects of either an acute administration (diazepam (i.p.) (AD) versus acute vehicle
GC/MS
The components of the lavender oil used in this study were analysed by GC/MS. Identification of the main peaks was by comparison of the retention times of the peaks with those of known standards, and then by confirmation with the NIST GC/MS library and also an in house monoterpene library. The main lavender components were identified as: linalyl acetate (43.98%), linalool (38.47%), lavandulyl acetate (4.81%), β-myrcene (1.44%), terpinen-4-ol (1.25%), β-terpineol (1.05%), cis-linalool oxide
Discussion
Of the two major components of lavender, linalool and linalyl acetate have shown pharmacological activity, both in terms of anaesthetic activity (Ghelardini et al., 1999), and an ability to depress locomotor activity in mice (Buchbauer et al., 1991). The aim here was to initially establish whether whole lavender oil odour had an anxiolytic effect in the gerbil EPM, with a future aim of examining the components of lavender in the model, should lavender oil odour prove to have anxiolytic effects
Conclusion
In conclusion it has been shown that prolonged exposure to lavender essential oil odour has mildly anxiolytic effects in the gerbil EPM. However, which components are responsible for these effects and by what mechanism remains to be elucidated. Future studies should include analysis of the separate components of lavender in the EPM. For example, linalool and linyl acetate which have been shown to cause sedation in mice (Buchbauer et al., 1993).
Aromatherapists often mention ‘synergy’ as the
Acknowledgements
The authors would like to thank the Faculty of Science technicians and Ms. K. Jordan and the Psychology technicians for their help and support in particular: Mr. C. Mullin for manufacturing the Elevated Plus Maze; Mr. J.C. Donnelly for his help with the GC–MS profiles; Ms. C. Woodcock and Mrs. R. Cley for all their, patient help and support while running the studies. This work was supported by strategic funding from the Department of Psychology, UCLAN, Preston, Lancashire, UK.
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