Interaction of Flomazenil with Anxiolytic Effects of <i>Citrus aurantium</i> L. Essential Oil on Male Mice

Abstract

Due to our previous findings about the role of GABAegic neurotransmission in anxiolytic effects of Citrus aurantium L. essential oil, we are now presenting flomazenil interaction with this herb, as an antagonist of benzodiazepines at GABA receptor. The study was performed on 84 male albino mice assigned to 14 groups of six. The animals were injected intraperitoneally with the Citrus aurantium L. essential oil for 5 days. On the fifth day, either normal saline or flomazenil (0.1 mg/kg) was injected to the experimental groups. Thirty minutes after the injection, all the groups were assessed for anxiety-related behavior by elevated plus-maze test. In groups receiving Citrus aurantium L. essential oil at doses of 2.5 and 5 percent, the time spent in the open arms increased significantly (P < 0.001). The injection of flumazenil alone induced anxiety quite clearly observed by decreasing the time or number of entries in open arms. As an antagonist of benzodiazepines at GABA receptor, flomazenil acted as a competitive antagonist for Citrus aurantium L. essential oil regarding the increment in the number of entries to the open arms and the time spent in the open arms (P < 0.001) compared to flumazenil. It can then be concluded that Citrus aurantium L. essential oil induces its anxiolytic effects like benzodiazepines, in the same site at GABA receptor.