Anxiolytic effects of menthol in elevated plus maze in mice: Involvement of the GABAergic pathway

Menthol is a monoterpene and the main component of essential oils of mint plants family. The sedative and anxiolytic effects of this compound have been reported, previously. However, mechanism of its anxiolytic action has not been elucidated. In this study, the effects of systemic administration of menthol in the open field test and elevated plus maze, also the possible mechanism of its anxiolytic effect in the elevated plus maze were investigated.

In the first phase of this study, mice in 8 separate groups received doses of 5, 10, 20, 50 and 100 mg/kg of menthol, diazepam and buspirone 30 minutes before the behavioral tests to assess anxiety. Based on the results, 50 mg/kg was determined as the effective dose of menthol. In the second stage, flumazenil as a benzodiazepine receptor antagonist and WAY 100635 as a serotonin receptor antagonist were applied to determine the underlying mechanism involved in the anxiolytic effect of menthol.

The present study showed that menthol, especially at the dose of 50 mg/kg, significantly reduced the number of lines, trimming and rearing behavior in the open field test, and increased the number of entries into the open arm and the time spent in the open arm, in the elevated plus maze (p < 0.05). Flumazenil administration reversed these effects in the elevated plus maze, whereas WAY100635 had no effect on it.

Menthol exerts its anxiolytic effects in the mouse elevated plus maze through the benzodiazepine not serotonin pathway.