Ethnopharmacological relevance: The use of lavender as sleep aid or hypnotic agent can be traced back as early as ancient Romans and Greeks. Yet, objective experimental data on whether and how lavender enhances sleep duration or/and sleep quality remain lacking. Aim of the study: We aimed to characterize the sleep-wake regulating effects of lavender in the mouse and to demonstrate the brain targets and neural circuits involved. Materials and methods: A self-made precise odor delivery system combined with chronic polysomnographic recordings was employed to assess the sleep-wake effects of inhalation with lavender essential oil (LEO, extracted from lavender) and its different constituents during the light and dark phases in free-moving C57BL/6J mice. Neuroviral labeling, in situ hybridization and pharmacogenetics were combined to identify the neural circuits and targets involved. Finally, an insomniac model of DL-4-Chlorophenylalanine (PCPA)-treated mice was established to examine the sleep-inducing potential of LEO. Results: We found that inhalation of LEO with a concentration at 25.0% during the light (inactive) phase significantly shortened the latency to non-rapid eye movement (NREM) sleep, increased the total amount of NREM sleep at the expense of wakefulness (W), and enhanced cortical EEG slow wave activities, notably delta power spectra density. We further identified linalool, d-limonene, 1,8-cineole, linalyl acetate and terpinene-4-ol as the major effective sleep-promoting monomer components. Importantly, we found that LEO no longer produced any of the above sleep-promoting effect following either nasal injection of zinc sulfate which interrupts the olfactory pathway, or pharmacogenetics silencing of central amygdala GABAergic neurons. Finally, LEO reestablished NREM sleep with short latency in PCPA-treated insomniac mice, effects comparable with those induced by a potent sedative diazepam.
[1]Lanzhou Univ, Sch Basic Med Sci, Dept Neurosci Anat Histol & Embryol, Key Lab Preclin Study New Drugs Gansu Prov, Lanzhou 730000, Peoples R China.
[2]Anshan Cent Hosp, Dept Anesthesiol, Anshan 114032, Peoples R China.
[3]Gansu Prov Hosp, Dept Pharm, Lanzhou 730000, Peoples R China.
[4]Shandong Second Med Univ, Sch Med Imaging, Weifang 261053, Peoples R China.
[5]Xian Med Univ, Dept Pharmacol, Xian 710021, Peoples R China.
[6]Univ Claude Bernard Lyon 1, Ctr Hosp Le Vinatier Neurocampus Michel Jouvet, Integrat Physiol Brain Arousal Syst, CRNL,INSERM,U1028,CNRS,UMR 5292, F-69675 Bron, France.
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