Neurochemical Journal

, Volume 7, Issue 1, pp 34–38 | Cite as

Co-administration of fluoxetine and Sildenafil has benefits in anxiety behavior in mice

  • S. Shahidi
  • N. Hashemi-FirouziEmail author
  • M. Mahmoodi
Experimental Articles


Fluoxetine, a selective serotonin reuptake inhibitor, has been widely prescribed drugs in psychiatry. However, it may produce controversial effects, including sexual dysfunction. Sildenafil, a phosphodiesterase inhibitor type 5, may reduce fluoxetine-induced behavior alterations, but its drug interaction profile has not been investigated. To evaluate the interaction between sildenafil and fluoxetine, we acutely or chronically administered adult male mice with intraperitoneal sildenafil (2 mg/kg); fluoxetine (10 mg/kg); a mixture of fluoxetine (10 mg/kg) and sildenafil (2 mg/kg); the anxiolytic benzodiazepine, diazepam (0.3 mg/kg); or saline, after which the mice were evaluated in an elevated plus-maze. The number of entries into the open arms, the time spent in the open arms, and the numbers of total entries into the arms were determined as measures of anxiety. Acute treatment with fluoxetine produced a behavioral profile consistent with anxiogenesis, while sildenafil produced an anxiolytic-like profile. Co-administration of fluoxetine with sildenafil reversed the anxiogenic effects of the former. In chronic treatment neither of drugs (alone) had any effects compared to controls. Their combination resulted in anxiolytic effect. These findings suggest that the anxiolytic sildenafil masked the effect of fluoxetine in the chronic experiment.


anxiety serotonin nitric oxide elevated plus-maze mice 


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  1. 1.
    Schneier, F.R., Expert. Opin. Pharmacother., 2011, vol. 12, pp. 615–625.PubMedCrossRefGoogle Scholar
  2. 2.
    Bagdy, G., Graf, M., Anheue, Z.E., Modos, E.A., and Kantor, S., Int. J. Neuropsychophar Macol., 2001, vol. 4, pp. 399–408.Google Scholar
  3. 3.
    Belzung, C., Le, Guisquet., A.M., Barreau, S., and Calatayud, F., Behav. Pharmacol., 2001, vol. 12, pp. 151–162.PubMedCrossRefGoogle Scholar
  4. 4.
    Volke, V., Wegener, G., and Vasar, E., J. Physiol. Pharmacol., 2003, vol. 54, pp. 653–560.PubMedGoogle Scholar
  5. 5.
    Workman, J.L., Trainor, B.C., Finy, M.S., and Nelson, R.J., Behav. Brain. Res., 2008, vol. 187, pp. 109–115.PubMedCrossRefGoogle Scholar
  6. 6.
    Chanrion, B., Mannoury la Cour, C., Bertaso, F., Lerner-Natoli, M., Freissmuth, M., Millan, M.J., et al., Proc. Natl. Acad. Sci. USA, 2007, vol. 104, pp. 8119–8124.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhang, J., Huang, X.Y., Ye, M.L., Luo, C.X., Wu, H.Y., et al., Behaviors. J. Neurosci., 2010, vol. 30, pp. 2433–2441.CrossRefGoogle Scholar
  8. 8.
    Kurt, M., Arik, A.C., and Celik, S., J. Basic. Clin. Physiol. Pharmacol., 2000, vol. 11, pp. 173–180.PubMedCrossRefGoogle Scholar
  9. 9.
    Zienowicz, M., Wisłowska-Stanek, A., Lehner, M., Taracha, E., et al., Pharmacol. Rep., 2006, vol. 58, pp. 115–119.PubMedCrossRefGoogle Scholar
  10. 10.
    File, S.E., Ouagazzal, A.M., Gonzalez, L.E., and Overstreet, D.H., Pharmacol. Biochem. Behav., 1999, vol. 62, pp. 695–701.PubMedCrossRefGoogle Scholar
  11. 11.
    Liebenberg, N., Harvey, B.H., Brand, L., and Brink, C.B., Behav. Pharmacol., 2010, vol. 21, pp. 540–547.PubMedCrossRefGoogle Scholar
  12. 12.
    Chiavegatto, S. and Nelson, R.J., Behavior. Horm. Behav., 2003, vol. 44, pp. 233–441.CrossRefGoogle Scholar
  13. 13.
    Nurnberg, H.G., Hensley, P.L., Gelenberg, A.J., et al., JAMA, 2003, vol. 289, pp. 56–64.PubMedCrossRefGoogle Scholar
  14. 14.
    Hosseini, M.M. and Yarmohammadi, H., Urol. Int., 2007, vol. 79, pp. 28–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Waldinger, M.D., J. Urol., 2002, vol. 168, pp. 2359–2367.PubMedCrossRefGoogle Scholar
  16. 16.
    Uthayathas, S., Karuppagounder, S.S., Thrash, B.M., et al., Pharmacol. Rep., 2007, vol. 59, pp. 150–163.PubMedGoogle Scholar
  17. 17.
    Solís, A. A., Bethancourt, J.A., and Britton, G.B., Psicothema, 2008, vol. 20, pp. 812–817.PubMedGoogle Scholar
  18. 18.
    Bryan-Lluka, L.J., Papacostasm, M.H., Paczkowski, F.A., and Wanstall, J.C., Br. J. Pharmacol., 2004,vol. 143, pp. 63–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Wegener, G., Volke, V., and Rosenberg, R., Br. J. Pharmacol., 2000, vol. 130, pp. 575–580.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhu, C.B., Hewlett, W.A., Francis, S.H., Corbin, J.D., and Blakely, R.D., Eur. J. Pharmacol., 2004, vol. 504, pp. 1–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Kurt, M., Bilge, S.S., Aksoz, E., et al., Pol. J. Pharmacol., 2004, vol. 56, pp. 353–357.PubMedGoogle Scholar
  22. 22.
    Bordukalo-Niksic, T., Mokrovic, G., Stefulj, J., Zivin, M., Jernej, B., and Cicin-Sain, L., Behav. Brain. Res., 2010, vol. 213, pp. 238–245.PubMedCrossRefGoogle Scholar
  23. 23.
    Dulawa, S.C., Holick, K.A., Gundersen, B., and Hen, R., Neuropsychopharmacology, 2004, vol. 29, pp. 1321–1330.PubMedCrossRefGoogle Scholar
  24. 24.
    Calixto, A.V., Duarte, F.S., Duzzioni, M., et al., Behav. Brain. Res., 2010, vol. 207, pp. 112–117.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  1. 1.Neurophysiology Research CenterHamadan University of Medical SciencesHamadanIran
  2. 2.Department of Biology, Faculty of School of Basic SciencesIslamic Azad University, Hamedan BranchHamedanIran
  3. 3.Department of Biology, Faculty of School of Basic SciencesIslamic Azad UniversityHamedanIran

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