title: Anxiolytic-like effect of lavender essential oil inhalation in mice: participation of serotonergic but not GABAA/benzodiazepine neurotransmission.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The objective of the present study was to determine whether the GABAA/benzodiazepine complex or serotonin neurotransmission mediates the anxiolytic-like effect of lavender essential oil.
  
  
  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. GABAA/benzodiazepine mediation was evaluated by pretreating the mice with the GABAA receptor antagonist picrotoxin before the marble burying test and [(3)H]flunitrazepam binding to the benzodiazepine site on the GABAA 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-HT1A 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-HT1A 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 GABAA receptor antagonist picrotoxin (0.5mg/kg) did not modify the behavioral effect of 5% lavender essential oil in the marble-burying test. Lavender essential oil also did not alter [(3)H]flunitrazepam binding to the benzodiazepine site on the GABAA receptor. Pretreatment with the serotonin 5-HT1A receptor antagonist WAY100635 (3mg/kg) blocked the anxiolytic-like effect of lavender essential oil and the 5-HT1A receptor agonist 8-OH-DPAT (3mg/kg). A combination of ineffective doses of 8-OH-DPAT (0.5mg/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.
authors.affiliation: Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR 81540-990, Brazil. leachioca@yahoo.com.br
authors.forename: Lea R
authors.initials: LR
authors.lastname: Chioca
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Ferro
authors.forename: Irinéia P
authors.initials: IP
authors.lastname: Baretta
authors.forename: Sara M
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Cássia R
authors.initials: CR
authors.lastname: Silva
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Estela M
authors.initials: EM
authors.lastname: Losso
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D027523:Lavandula; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009822:Oils, Volatile / Q000008:administration & dosage*; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010938:Plant Oils / Q000008:administration & dosage*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D020230:Serotonin Syndrome; D009435:Synaptic Transmission
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014151:Anti-Anxiety Agents; D003975:Diazepam; D005445:Flunitrazepam; D058787:GABA-A Receptor Antagonists; D009822:Oils, Volatile; D010852:Picrotoxin; D010879:Piperazines; D010938:Plant Oils; D011725:Pyridines; D011963:Receptors, GABA-A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C045718:lavender oil