Citral, a monoterpene which is a part of the essential oil of several medicinal plants, is generally regarded as safe for human and animal consumption. Studies have introduced citral as a functional component of some essential oils in anxiolytic and antidepressant therapies; however, the neuropharmacological characteristics of citral have not yet been reported. In the present study, we evaluated the anxiolytic activities of citral in comparison to two standard anxiolytics, diazepam and buspirone, in Swiss albino mice by intraperitoneal administration of 1, 2, 5, 10, and 20 mg/kg using elevated plus maze (EPM) and openfeld test (OFT). Moreover, we also examined whether the GABAA–benzodiazepine and 5-HT1A receptor are involved in the anxiolytic-like efects of citral by pretreatment with fumazenil and WAY-100635, respectively. Citral dose-dependently decreased the number of border crossings and time spent in borders, and also the number of grooming and rearing in OFT without altering the exploratory behavior of mice. In the EPM, this monoterpene led to a signifcant increase in number of entries in open arms and time spent in open arms, as well as a decrease in time spent in closed arms. Pretreatment with fumazenil and WAY-100635 both could reverse the anxiolytic efects of the citral in the EPM. These results suggest that anxiolytic activity of citral occurs via the GABAA and 5-HT1A receptor modulation.
