Interaction of Flomazenil with Anxiolytic Effects of Citrus aurantium L. Essential Oil on Male Mice


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.

Share and Cite:

Adibi, L. , Khosravi, M. , Khakpour, S. , Sahraei, H. and Jahromy, M. (2015) Interaction of Flomazenil with Anxiolytic Effects of Citrus aurantium L. Essential Oil on Male Mice. Pharmacology & Pharmacy, 6, 41-46. doi: 10.4236/pp.2015.62006.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Bueno, C.H., Zangrossi Jr., H. and Viana, M.B. (2005) The Inactivation of the Basolateral Nucleus of the Rat Amygdala Has an Anxiolytic Effect in the Elevated T-Maze and Light/Dark Transition Tests. Brazilian Journal of Medical and Biological Research, 38, 1697-1701.
[2] Zarrindast, M.R., Torabi, M., Rostami, P. and Fazli-Tabaei, S. (2006) The Effects of Histaminergic Agents in the Dorsal Hippocampus of Rats in the Elevated Plus-Maze Test of Anxiety. Pharmacology Biochemistry and Behavior, 85, 501-506.
[3] Andreasen, N.C. (2004) Acute and Delayed Posttraumatic Stress Disorder: A History and Some Issues. American Journal of Psychiatry, 161, 1321-1323.
[4] Gray, J.A. and McNaughton, N. (2000) The Neuropsychology of Anxiety. 2nd Edition, Oxford Medical Publications, Oxford.
[5] Taylor, M, Bhagwagar, Z., Cowen, P.J. and Sharp, T. (2003) GABA and Mood Disorders. Psychological Medicine, 33, 3873-3893.
[6] Chebib, M. and Johnston, G.A.R. (2000) GABA-Activated Ligand Gated Ion Channels: Medicinal Chemistry and Molecular Biology. Journal of Medicinal Chemistry, 43, 1427-1447.
[7] Carvalho-Freitas, M.I. and Costa, M. (2002) Anxiolytic and Sedative Effects of Extracts and Essential Oil from Citrus aurantium L. Biological & Pharmaceutical Bulletin, 25, 1629-1633.
[8] Re, L., Barocci, S., Sonnino, S., et al. (2000) Linalool Modifies the Nicotinic Receptor-Ion Channel Kinetics at the Mouse Neuromuscular Junction. Neurochemical Research, 42, 177-181.
[9] Silva Brum, L.F., Emanuelli, T., Souza, D.O., et al. (2001) Effects of Linalool on Glutamate Release and Uptake in Mouse Cortical Synaptosomes. Neurochemical Research, 26, 191-194.
[10] Fuster, J.M. (2000) The Prefrontal Cortex—An Update: Time Is of the Essence. Neuron, 30, 319-333.
[11] Johnston, G.A.R. (2005) GABAA Receptor Channel Pharmacology. Current Pharmaceutical Design, 11, 1867-1885.
[12] Lader, M.B. and Morton, S.V. (1992) A Pilot Study of the Effects of Flumazenil on Symptoms Persisting after Benzodiazepine Withdrawal. Journal of Psychopharmacology, 6, 19-28.
[13] Votey, S.R., Bosse, G.M., Bayer, M.J. and Hoffman, J.R. (1991) Flumazenil: A New Benzodiazepine Antagonist. Annals of Emergency Medicine, 20, 181-188.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.