Involvement of Serotonergic System and Magnesium on Anxiolytic Effects of Pomegranate in Male Mice

Abstract

The anxiolytic activities of Punica granatum L. fruit juice (PGFJ) in various validated animal models of anxiety and amnesia have been recently reported in mice. Similarly, anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in some studies. Buspirone is an anxiolytic psychoactive drug with known effects on 5-HT1A receptors that its action is not related to benzodiazepines. The purpose of the present study was to examine interactions between PGFJ, magnesium (Mg) and buspirone as a partial agonist of 5-HT1A receptors in producing anxiolytic-like activity in the elevated plus maze in mice. The anxiolytic-like effect of PGFJ (5, 10 and 20 ml/kg, orally), buspirone (5 mg/kg, i.p), Mg (50 mg/kg, orally) and their interactions were evaluated after ten days’ treatment. PGFJ given at all doses induced an anxiolyticlike effect significantly increasing the percentage of the time spent in the open arms, and the percentage of the open arm entries, in a dose-dependent manner. Buspirone showed anxiolytic effect after ten days; however, its effect was roughly comparable to the effect of PGFJ 5 ml/kg. Buspirone in combination with PGFJ (5 ml/kg), did produce more effect compared to buspirone alone and nearly in the range of PGFJ 5 ml/kg response. Also, Mg induced an anxiolytic-like effect that was more than effects observed by buspirone 5 mg/kg. However, binary application of buspirone and Mg showed anxiolytic effects more than buspirone, alone. In another group, Mg in combination with PGFJ (5 ml/kg), produced more anxyolitic effects compared to either Mg or PEF alone. It can be concluded that Pomegranate anxyolitic-like effect is dependent on interactions with both GABAergic (related to Mg) and serotonergic (5-HT1A) systems.

Share and Cite:

Jahromy, M. , Shariatifar, A. , Samiee, S. , Vaziri, M. , Shahraki, M. and Dara, S. (2014) Involvement of Serotonergic System and Magnesium on Anxiolytic Effects of Pomegranate in Male Mice. World Journal of Neuroscience, 4, 293-298. doi: 10.4236/wjns.2014.44032.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th Edition, American Psychiatric Publishing, Arlington, MA, 189-195.
[2] Patel, G. and Fancher, T.L. (2013) In the Clinic. Generalized Anxiety Disorder. Annals of Internal Medicine, 159, Article ID: ITC6-1. http://dx.doi.org/10.7326/0003-4819-159-11-201312030-01006
[3] Jurenka, J. (2008) Therapeutic Applications of Pomegranate (Punica granatum L.): A Review. Alternative Medicine Review, 13, 128-144.
[4] Lydiard, R.B. (2003) The Role of GABA in Anxiety Disorders. The Journal of Clinical Psychiatry, 64, 21-27.
[5] Ryan, M.F. (1991) The Role of Magnesium in Clinical Biochemistry: An Overview. Annals of Clinical Biochemistry, 28, 19-26. http://dx.doi.org/10.1177/000456329102800103
[6] Cardoso, C.C., Lobato, K.R., Binfaré, R.W., Ferreira, P.K., Rosa, A.O., Santos, A.R.S. and Rodrigues, A.L.S. (2009) Evidence for the Involvement of the Monoaminergic System in the Antidepressant-Like Effect of Magnesium. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 33, 235-242.
http://dx.doi.org/10.1016/j.pnpbp.2008.11.007
[7] Poleszak, E., Szewczyk, B., Kêdzierska, E., Wlaz, P., Pilc, A. and Nowak, G. (2004) Antidepressantand AnxiolyticLike Activity of Magnesium in Mice. Pharmacology Biochemistry and Behavior, 78, 7-12.
http://dx.doi.org/10.1016/j.pbb.2004.01.006
[8] Poleszak, E., Wlaz, P, Kêdzierska, E., Nieoczym, D., Wyska, E., Szymura-Oleksiak, J., Fidecka, S., et al. (2006) Immobility Stress Induces Depression-Like Behavior in the Forced Swim Test in Mice: Effect of Magnesium and Imipramine. Pharmacological Reports, 58, 746-752.
[9] Dunlop, B.W. and Davis, P.G. (2008) Combination Treatment with Benzodiazepines and SSRIs for Comorbid Anxiety and Depression: A Review. Prim Care Companion Journal of Clinical Psychiatry, 10, 222-228.
http://dx.doi.org/10.4088/PCC.v10n0307
[10] Fulton, B. and Brogden, R.N. (1997) Buspirone. CNS Drugs, 7, 68-88.
http://dx.doi.org/10.2165/00023210-199707010-00007
[11] Buspirone monoFigure. Retrieved 2011-08-27. www.drugs.com/monograph/buspirone-hydrochloride.html
[12] Jadhav, S.A., Gaikwad, R.V., Gaonkar, R.K., Thorat, V.M., Gursale, S.C. and Balsara, J.J. (2008) Dose-Dependent Response of Central Dopaminergic Systems to Buspirone in Mice. Indian Journal of Experimental Biology, 46, 704-714.
[13] Cohn, J.B., Rickels, K. and Steege, J.F. (1989) A Pooled, Double-Blind Comparison of the Effects of Buspirone, Diazepam and Placebo in Women with Chronic Anxiety. Current Medical Research and Opinion, 11, 304-320.
http://dx.doi.org/10.1185/03007998909115213
[14] Poleszak, E., Wlaz, P., Kêdzierska, E., Nieoczym, D., Wróbel, A., Fidecka, S., Pilc, A. and Nowak, G. (2007) NMDA/ Glutamate Mechanism of Antidepressant-Like Action of Magnesium in Forced Swim Test in Mice. Pharmacology Biochemistry and Behavior, 88, 158-164.
http://dx.doi.org/10.1016/j.pbb.2007.07.018
[15] Poleszak, E., Wlaz, P, Wróbel, A., Dybala, M., Sowa, M., Fidecka, S., Pilc, A. and Nowak, G. (2007) Activation of the NMDA/Glutamate Receptor Complex Antagonizes the NMDA Antagonist-Induced Antidepressant-Like Effects in the Forced Swim Test. Pharmacological Reports, 59, 595-600.
[16] Lister, R.G. (1987) The Use of a Plus-Maze to Measure Anxiety in the Mouse. Psychopharmacology, 92, 180-185.
http://dx.doi.org/10.1007/BF00177912
[17] Korwar, P.G. and Beknal, A. (2012) Anti-Anxiety Activity of Punica granatum Fruit Juice in Rats. International Journal of Pharmaceutical Invention, 2, 22-30.
[18] Dunn, R.W., Corbett, R. and Fielding, S. (1989) Effects of 5-HTlA Receptor Agonist and NMDA Receptor Antagonist in the Social Interaction Test and the Elevated plus Maze. European Journal of Pharmacology, 169, 1-10.
http://dx.doi.org/10.1016/0014-2999(89)90811-X
[19] Poleszak, E. (2008) Benzodiazepine/GABA(A) Receptors Are Involved in Magnesium-Induced Anxiolytic-Like Behavior in Mice. Pharmacological Reports, 60, 483-489.

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.