Anxiolytic-like effect of lavender essential oil inhalation in mice: Participation of serotonergic but not GABAA/benzodiazepine neurotransmission

Ethnopharmacological relevance

Lavandula angustifolia (lavender) inhalation has been used in folk medicine for the treatment of anxiety, and clinical and animal studies have corroborated its anxiolytic effect, although its mechanism of action is still not fully understood.

Aims of the study

The objective of the present study was to determine whether the GABA_A/benzodiazepine complex or serotonin neurotransmission mediates the anxiolytic-like effect of lavender essential oil.

Materials and methods

Male Swiss mice were subjected to the marble-burying test after being exposed to the aroma of lavender essential oil (1–5%), amyl acetate (5%; used as a behaviorally neutral odor), or distilled water for 15 min via inhalation. Additionally, the effect of 5% lavender essential oil was also evaluated in mice subjected to the elevated plus maze. GABA_A/benzodiazepine mediation was evaluated by pretreating the mice with the GABA_A receptor antagonist picrotoxin before the marble burying test and ³H]flunitrazepam binding to the benzodiazepine site on the GABA_A receptor. Serotonergic mediation was studied by pretreating the mice with O-methyl-3H]-N-(2-4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635), a serotonin 5-HT_1A receptor antagonist before the marble burying test. We also evaluated changes in the pharmacologically induced serotonin syndrome and the effects of combined administration of subeffective doses of lavender essential oil and the 5-HT_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).

Results

Lavender essential oil (1–5%) decreased the number of marbles buried compared with the control and amyl acetate groups. In the elevated plus maze, 5% lavender essential oil inhalation increased the percentage of time spent on and number of entries into the open arms compared with controls. No effect was seen in the number of closed arm entries or number of beam interruptions in the automated activity chamber. Pretreatment with the GABA_A receptor antagonist picrotoxin (0.5 mg/kg) did not modify the behavioral effect of 5% lavender essential oil in the marble-burying test. Lavender essential oil also did not alter ³H]flunitrazepam binding to the benzodiazepine site on the GABA_A receptor. Pretreatment with the serotonin 5-HT_1A receptor antagonist WAY100635 (3 mg/kg) blocked the anxiolytic-like effect of lavender essential oil and the 5-HT_1A receptor agonist 8-OH-DPAT (3 mg/kg). A combination of ineffective doses of 8-OH-DPAT (0.5 mg/kg) and lavender essential oil (0.1%) reduced the number of marbles buried. Finally, 5% lavender essential oil attenuated the serotonin syndrome induced by 40 mg/kg fluoxetine plus 80 mg/kg 5-hydroxytryptophan.

Conclusions

These results indicate an important role for the serotonergic system in the anxiolytic-like effect of lavender essential oil.