Evidence for the involvement of the GABAergic, but not serotonergic transmission in the anxiolytic-like effect of bisabolol in the mouse elevated plus maze

Naunyn Schmiedebergs Arch Pharmacol. 2017 Oct;390(10):1041-1046. doi: 10.1007/s00210-017-1405-0. Epub 2017 Jul 20.


Bisabolol (α-(-)-bisabolol) is a sesquiterpene which is a part of the essential oil of a variety of plants, but its common source is German chamomile. Several bioactivities including anti-inflammatory, anti-nociceptive, and anti-tumor effects were attributed to bisabolol. However, the neuropharmacological properties of bisabolol have not yet been reported. The present study evaluated behavioral effects of bisabolol using elevated plus maze (EPM), open field test (OFT), and rotarod test. Moreover, this study also examined whether the 5-HT1A and GABAA-benzodiazepine receptor systems are involved in the anxiolytic-like effects of bisabolol. After acute intraperitoneal treatment with bisabolol at the doses of 0.5, 1, 2, 5, and 10 mg/kg, OFT, EPM, and rotarod were utilized for investigating behavioral effects. Flumazenil, a benzodiazepine receptor antagonist, and WAY-100635, a 5-HT1A receptor antagonist, were used to determine the action mechanism in the EPM. Bisabolol especially at the dose of 1 mg/kg was effective in increasing the total number of entries and time spent in the open arms of EPM while number of rearing and grooming in OFT was decreased in comparison to the control. In the rotarod, permanence time was decreased in the mice treated with the high doses of bisabolol. Pretreatment with flumazenil, but not WAY-100635, was able to reverse the effect of bisabolol 1 mg/kg in the EPM, indicating that the anxiolytic-like activity of bisabolol occurs via the GABAergic but not serotonergic transmission. The present study supports the idea that bisabolol may mediate its anxiolytic-like and sedative mechanisms involving GABAA receptors.

Keywords: Anxiolytic-like; Bisabolol; GABAergic modulators; Locomotor activity; Sedative; Sesquiterpene.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anti-Anxiety Agents / therapeutic use
  • Anxiety / drug therapy*
  • Anxiety / psychology
  • Dose-Response Relationship, Drug
  • GABA-A Receptor Agonists / pharmacology
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Mice
  • Monocyclic Sesquiterpenes
  • Receptor, Serotonin, 5-HT1A* / physiology
  • Receptors, GABA-A* / physiology
  • Rotarod Performance Test / methods
  • Serotonin Antagonists / pharmacology
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use


  • Anti-Anxiety Agents
  • GABA-A Receptor Agonists
  • Monocyclic Sesquiterpenes
  • Receptors, GABA-A
  • Serotonin Antagonists
  • Sesquiterpenes
  • Receptor, Serotonin, 5-HT1A
  • bisabolol