j ad vetbio sci tech Journal of Advances in VetBio Science and Techniques 2548-1150 İlker ÇAMKERTEN 10.31797/vetbio.1383152 Veterinary Pharmacology Veteriner Farmakoloji The antidepressant efficacy of flurbiprofen in mice: Behavioural assessment https://orcid.org/0000-0002-3491-5351 Alberfkani Naktal https://orcid.org/0000-0003-1618-0678 Naser Ahmed 04 30 2024 9 1 59 64 10 31 2023 04 16 2024 Copyright © 2016, Journal of Advances in VetBio Science and Techniques 2016 Journal of Advances in VetBio Science and Techniques

Flurbiprofen is a nonsteroidal anti-inflammatory medication (NSAID). The psychological effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is a source of contention based on clinical and experimental evidence. As a result, the goal of our study was to assess the antidepressant effects of various flurbiprofen doses in mice. We evaluated the effect of oral administration of flurbiprofen at 10, 20, and 40 mg/kg in the tail suspension and forced swimming tests after 1 h of treatment. Fluoxetine (10 mg/kg, i.p.) was used as a positive control. Flurbiprofen at 40 mg/kg showed a significant antidepressant effect, which was revealed by a significant decrease in immobility time compared with the control group, with the group administered flurbiprofen at 10 mg/kg, and with the group given flurbiprofen at 20 mg/kg in the tail suspension test. Flurbiprofen at 40 mg/kg showed an antidepressant effect, which was revealed by a significant decrease in immobility time compared with the control group and with the group given flurbiprofen at 10 mg/kg. Flurbiprofen at 20 mg/kg had a minimal antidepressant effect in the swimming forced test, which was reflected by a non-significant decrease in immobility time compared with the control group. In conclusion, our results showed that relatively high therapeutic doses of flurbiprofen might have an antidepressant effect in a mouse model, and we recommended conducting other in vivo studies to clarify the variation in dose response.

 Flurbiprofen Antidepressant Mice Abbas, M.G, Hirotaka, S., Shingo, S., Mari, H., Tsuyoshi, M., & Takeshi, S. (2015). Comprehensive Behavioral Analysis of Male Ox1r−/− Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior. Frontiers in Behavioral Neuroscience, 9: 324. https://doi.org/10.3389/fnbeh .2015.00324 Alberifki, N. M, & Ahmed, S. N. (2023). Flurbiprofen: Determination of Safety Profile, Analgesic Effect, and Interaction with Lipoic Acid in Murine. Iraqi Journal of Veterinary Sciences, 37 (2): 447–52. https://doi. org/10.33899/ijvs.2023.136615.2599 Alboni, S., Cristina, B., Giacomo, C., Fabio, T., & Nicoletta, B. (2018). Neither All Anti-Inflammatory Drugs nor All Doses Are Effective in Accelerating the Antidepressant-like Effect of Fluoxetine in an Animal Model of Depression. Journal of Affective Disorders, 235: 124–28. https://doi.org/10.1016/j.jad.2018.04. 063 Albrefkani, N., & Ahmed, N. (2023). Evaluation of the Anticonvulsant Properties of Flurbiprofen in Pilocarpine-Induced Convulsions in Mice. Baghdad Journal of Biochemistry and Applied Biological Sciences,4(1):1-9. https://doi.org/10.47419/bjbabs. v4i01.182 Bay-Richter, C., & Gregers, W. (2022). Antidepressant Effects of NSAIDs in Rodent Models of Depression - A Systematic Review. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.909981 Dantzer, R., Emmanuelle, E. W., Ljubisa, V., & Raz, Y. (1999). Cytokines, Stress, and Depression. Cytokines, Stress, and Depression, 317–29. https://doi.org/10.1007/978-0-585-37970-8_17 Dunn, A. J., Jianping, W., & Tetsuya, A. (1999). Effects of Cytokines on Cerebral Neurotransmission. Cytokines, Stress, and Depression, 117–27. https://doi.org/10.1007/978-0-585-37970-8_8 Höglund, E., Øyvind, Ø., & Svante, W. (2019). Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review. Frontiers in Endocrinology, 158. https://doi.org/ 10.3389/fendo.2019.00158 Matsuda, I., Hirotaka, S., Nobuyuki, Y., Tsuyoshi, M., &Atsu, A. (2016). Comprehensive Behavioral Phenotyping of a New Semaphorin 3 F Mutant Mouse. Molecular Brain, 9 (1): 1–13. https://doi.org/10.1186/ s13041-016-0196-4 Miller, D. B., & James, P. O. (2005). Depression, Cytokines, and Glial Function. Metabolism, 54 (5): 33–38. https://doi.org/10.1016/j.metabol.2005.01.011 Naser, A. S., & Albrefkani, N. (2023). Assessment of Anxiolytic-like Effects of Acute and Chronic Treatment of Flurbiprofen in Murine. Journal of Ideas in Health, 6 (1): 814–19. https://doi.org/ 10.47108/jidhealth.Vol6.Iss1.268 Norden, D. M., Donna, O. M., Sabahattin, B., Raymond, D. D., Peter, J., Jonathan, P. G., &Loren, E. W. (2015). Ibuprofen Ameliorates Fatigue-and Depressive-like Behavior in Tumor-Bearing Mice. Life Sciences, 143: 65–70. https://doi.org/10.1016/ j.lfs.2015.10.020 Onouchi, T., Katsunori, K., Kazuyoshi, S., Atsushi, S., Ron, S., Chiho, S., Masafumi, K., Keizo, T., Ryuji, N., & Akiko, I. (2014). Targeted Deletion of the C-Terminus of the Mouse Adenomatous Polyposis Coli Tumor Suppressor Results in Neurologic Phenotypes Related to Schizophrenia. Molecular Brain, 7 (1): 1–14. https://doi.org/10.1186/1756-6606-7-21 Răducanu, I., Ana, S., Gabriel, P., CRISTINA, I., ANDREEA, A., &Ion, F. (2012). Assessing Depressive Effect of Ketoprofen and Its Mechanism of Action Using the Forced Swimming Test in Mice. Farmacia, 60 (5): 759–66. Rush, A. J., Helena, C. K., Harold, A. S., Maurizio, F., Madhukar, H. T., Ellen, F., Philip, T. N, Michael, E. T., Alan, J., G., &David, J. K. (2006). Report by the ACNP Task Force on Response and Remission in Major Depressive Disorder. Neuropsychopharmacology, 31 (9): 1841–53. https://doi.org/10.1038/sj.npp.1301131 Salmani, H., Mahmoud, H., Yousef, B., &Zahra, S. (2021). The Brain Consequences of Systemic Inflammation Were Not Fully Alleviated by Ibuprofen Treatment in Mice. Pharmacological Reports , 73 (1): 130–42. https://doi.org/10.1007/s43440-020-00141-y Schiepers, O. J. G., Marieke, C., &Michael, M.( 2005). Cytokines and Major Depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29 (2): 201–17. https://doi.org/10.1016/j.pnpbp.2004 .11.003 Svenningsson, P., Karima, C., Ilan, R., Marc, F., Xiaoqun, Z., Malika, E., Jean-Marie, V., George, G. N., &Paul, G. (2006). Alterations in 5-HT1B Receptor Function by P11 in Depression-like States. Science, 311 (5757): 77–80. https://doi.org/10.1126/science.1117571 Ueno, H., Yu, T., Shinji, M., Kenta, W., Yosuke, M., Motoi, O., &Takeshi, I. (2022). Effect of Simultaneous Testing of Two Mice in the Tail Suspension Test and Forced Swim Test. Scientific Reports ,12 (1): 1–14. https://doi.org/10.1038/s41598-022-12986-9 Umemura, M., Tae, O., Ayako, M., Haruo, N., Keizo, T., Tsuyoshi, M., &Yuji, T. (2017). Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice. Frontiers in Behavioral Neuroscience, 11: 125. https://doi.org/10.3389/fnbeh .2017.00125 Warner-Schmidt, J.L., Emily, Y. C., Xiaoqun, Z., John, J. M., Alexei, M., Per, S., & Paul, G. (2010). A Role for P11 in the Antidepressant Action of Brain-Derived Neurotrophic Factor. Biological Psychiatry, 68 (6): 528–35. https://doi.org/10.1016/j.biopsych. 2010.04.029 Warner-Schmidt, J. L., Marc, F., Abigail, M., Emily, Y. C., Hongshi, Q., Per ,S., & Paul, G. (2009). Role of P11 in Cellular and Behavioral Effects of 5-HT4 Receptor Stimulation. Journal of Neuroscience, 29 (6): 1937–46. https://doi.org/10.1523/JNEUROSCI.5343-08.2009 Warner-Schmidt, J. L., Kimberly, E. V., Emily, Y. C., John, J. M., &Paul, G. (2011). Antidepressant Effects of Selective Serotonin Reuptake Inhibitors (SSRIs) Are Attenuated by Antiinflammatory Drugs in Mice and Humans. Proceedings of the National Academy of Sciences, 108 (22): 9262–67. https://doi.org/10 .1073/pnas.1104836108 Wilson, C. J., Caleb, E. F., &Harvey, J. C. (2002). Cytokines and Cognition—the Case for a Head‐to‐toe Inflammatory Paradigm. Journal of the American Geriatrics Society, 50 (12): 2041–56. https://doi.org/10.1046/j.1532-5415.2002.50619.x Yang, S., Hai-Yang, Y., Dan-Yu, K., Zhan-Qiang, M., Rong, Q., Qiang, F., &Shi-Ping, M. (2014). Antidepressant-like Effects of Salidroside on Olfactory Bulbectomy-Induced pro-Inflammatory Cytokine Production and Hyperactivity of HPA Axis in Rats. Pharmacology Biochemistry and Behavior, 124: 451–57. https://doi.org/10.1016/j.pbb.2014.07.015 Young, J. J., Davide, B., &Nunzio, P. (2014). A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder. Journal of Affective Disorders, 169: 15–20. https://doi.org/10. 1016/j.jad.2014.07.032 Zhou, L., Tian, W., Yawen, Y., Mingan, L., Xiaohui, W. S., Yunjie, W., Ce, Z., &Fenghua, F. (2022). The Etiology of Poststroke-Depression: A Hypothesis Involving HPA Axis. Biomedicine & Pharmacotherapy, 151: 113146. https://doi.org/10. 1016/j.biopha.2022.113146