Skip to main content Skip to main navigation menu Skip to site footer

Effect of probiotics as adjuvant therapy of antidepressants in male Wistar rats with anhedonia behavior


Link of Video Abstract :


Background: Depression is one of the most common causes of disability in the world, and one third of patients do not respond to currently available antidepressants, so a strategy is needed in its management. There have been many studies looking for a relationship between the role of the gut and mental health. Probiotics are the focus of much research in the field of psychiatry today due to their alleged role in improving mental health through gut health.

Methods: This research was a true experimental study with a posttest-only design with a control group design. Brain-derived neurotrophic factor (BDNF) plasma levels, serum serotonin (ST) serum levels, and sucrose preference test (SPT) values were analysed in 39 male Wistar rats with anhedonic behavior.

Results: Average BDNF plasma level in treatment group was 1.63 ng/mL with a standard deviation of 0.56 ng/mL, while the mean BDNF plasma level in control group was 0.89 ng/mL with a standard deviation of 0.46 ng/mL. There was a significant difference in that the BDNF plasma levels in the control group were lower than in the treatment group, with a p<0.001 (CI = 95%). The median ST serum level in the treatment group was 25.78 with an IQR of 9.61 ng/mL, while the median ST serum level in the control group was 7.5 with an IQR of 0.38 ng/mL. Statistically, the difference is significant from the p value <0.001. The median SPT score in the treatment group was 84.5 with an interquartile range (IQR) of 12%, while the median SPT value in the control group was 67 with an IQR of 8%.

Conclusion: There was an effect of probiotics as an adjuvant antidepressant therapy in male Wistar rats with anhedonic behavior.


  1. Šalamon Arčan I, Kouter K, Videtič Paska A. Depressive disorder and antidepressants from an epigenetic point of view. World J Psychiatry. 2022;12(9):1150-1168.
  2. Malla A, Joober R, Garcia A. "Mental illness is like any other medical illness": a critical examination of the statement and its impact on patient care and society. J Psychiatry Neurosci. 2015;40(3):147-150.
  3. Park SC, Jang EY, Xiang YT, et al. Network analysis of the depressive symptom profiles in Asian patients with depressive disorders: Findings from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD). Psychiatry Clin Neurosci. 2020;74(6):344-353.
  4. Machmutow K, Meister R, Jansen A, et al. Comparative effectiveness of continuation and maintenance treatments for persistent depressive disorder in adults. Cochrane Database Syst Rev. 2019;5(5):CD012855.
  5. van der Feltz-Cornelis C, Allen SF, Holt RIG, Roberts R, Nouwen A, Sartorius N. Treatment for comorbid depressive disorder or subthreshold depression in diabetes mellitus: Systematic review and meta-analysis. Brain Behav. 2021;11(2):e01981.
  6. Kheng K, Liu Y wenn, Kuo P hsiu, Chung Y chu E, Lu M liang. Effect of probiotics on depressive symptoms : A meta-analysis of human studies. Psychiatry Res. 2019;112568.
  7. Liang S, Wu X, Jin F. Gut-brain psychology: rethinking psychology from the microbiota-gut-brain axis. Front Integr Neurosci. 2018;12:33.
  8. Wedari NLPH, Sukrama IDM, Budayanti NNS, Sindhughosa DA, Prabawa, IPY, Manuaba IBAP. One Health concept and role of animal reservoir in avian influenza: a literature review. Bali Medical Journal. 2021;10(2):515-520.
  9. Porter GA, O'Connor JC. Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime?. World J Psychiatry. 2022;12(1):77-97.
  10. Yong SJ, Tong T, Chew J, Lim WL. Antidepressive mechanisms of probiotics and their therapeutic potential. Front Neurosci. 2020;13:1361.
  11. Zong Y, Chen T, Dong H, Zhu L, Ju W. Si-Ni-San prevents reserpine-induced depression by inhibiting inflammation and regulating CYP450 enzymatic activity. Front Pharmacol. 2020;10:1518.
  12. Cheung RYM, Cheng WY, Li JB, Lau EYH, Chung KKH. Mothers' and fathers' stress and severity of depressive symptoms during the COVID-19 pandemic: actor-partner effects with parental negative emotions as a moderator. BMC Psychol. 2022;10(1):294.
  13. Carniel BP, da Rocha NS. Brain-derived neurotrophic factor (BDNF) and inflammatory markers: Perspectives for the management of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2021;108:110151.
  14. Hacimusalar Y, Eşel E. Suggested biomarkers for major depressive disorder. Noro Psikiyatr Ars. 2018;55(3):280-290.
  15. Klein AB, Williamson R, Santini MA, et al. Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol. 2011;14(3):347-353.
  16. Lim DW, Um MY, Han T, Lee J, Kim YT, Cho S, et al. Standardized Citrus unshiu peel extract ameliorates dexamethasone-induced neurotoxicity and depressive-like behaviors in mice. Metab Brain Dis. 2018;33(6):1877–86.
  17. Skupio U, Tertil M, Sikora M, Golda S, Wawrzczak-Bargiela A, Przewlocki R. Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: Relevance to depression. Neuroscience. 2015;286:141–50.
  18. Wu J, Li J, Gaurav C, Muhammad U, Chen Y, Li X, et al. CUMS and dexamethasone induce depression-like phenotypes in mice by differentially altering gut microbiota and triggering macroglia activation. Gen psychiatry. 2021;34(6):e100529.
  19. Ghasemi A, Jeddi S, Kashfi K. The laboratory rat: Age and body weight matter. EXCLI J. 2021;20:1431–45.
  20. Rao N. The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet. 2007;46(4):281–90.
  21. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002;109(2):143-148.
  22. Satomura E, Baba H, Nakano Y, Maeshima H, Suzuki T, Arai H. Correlations between brain-derived neurotrophic factor and clinical symptoms in medicated patients with major depression. J Affect Disord. 2011;135(1-3):332-335.
  23. Bouckaert F, Dols A, Emsell L, et al. Relationship between hippocampal volume, serum BDNF, and depression severity following electroconvulsive therapy in late-life depression. Neuropsychopharmacology. 2016;41(11):2741-2748.
  24. Aydemir O, Deveci A, Taneli F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(2):261-265.
  25. Ji M, Niu S, Mi H, Jang P, Li Y, Hu W. Antidepressant functions of Jie Yu Chu Fan capsule in promoting hippocampal nerve cell neurogenesis in a mouse model of chronic unpredictable mild stress. Ann Transl Med. 2020;8(16):1020.
  26. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558(Pt 1):263-275.
  27. Tu F, Pang Q, Huang T, Zhao Y, Liu M, Chen X. Apigenin ameliorates post-stroke cognitive deficits in rats through histone acetylation-mediated neurochemical alterations. Med Sci Monit. 2017;23:4004-4013.
  28. Sun J, Wang F, Hu X, et al. Clostridium butyricum attenuates chronic unpredictable mild stress-induced depressive-like behavior in mice via the gut-brain axis. J Agric Food Chem. 2018;66(31):8415-8421.
  29. Hao Z, Wang W, Guo R, Liu H. Faecalibacterium prausnitzii (ATCC 27766) has preventive and therapeutic effects on chronic unpredictable mild stress-induced depression-like and anxiety-like behavior in rats. Psychoneuroendocrinology. 2019;104:132-142.
  30. Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans : a systematic review. Ann Gen Psychiatry. 2017;1–10.
  31. Liu QF, Kim HM, Lim S, et al. Effect of probiotic administration on gut microbiota and depressive behaviors in mice. Daru. 2020;28(1):181-189.
  32. Bravo JA, Forsythe P, Chew M V., Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050–5.
  33. Chahwan B, Kwan S, Isik A, Hemert S Van, Burke C, Roberts L. Journal of A ff ective Disorders Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms. J Affect Disord. 2019;253(February):317–26.
  34. Abildgaard A, Elfving B, Hokland M, Wegener G, Lund S. Probiotic treatment reduces depressive-like behaviour in rats independently of diet. Psychoneuroendocrinology. 2017;79:40–8.
  35. Suda K, Matsuda K. How microbes affect depression: underlying mechanisms via the gut-brain axis and the modulating role of probiotics. Int J Mol Sci. 2022;23(3):1172.
  36. Tillmann S, Wegener G. Probiotics reduce risk-taking behavior in the Elevated Plus Maze in the Flinders Sensitive Line rat model of depression. Behav Brain Res. 2019;359:755–62.
  37. Neufeld KA, Kay S, Bienenstock J. Mouse strain affects behavioral and neuroendocrine stress responses following administration of probiotic lactobacillus rhamnosus JB-1 or traditional antidepressant fluoxetine. Front Neurosci. 2018;12:294.
  38. Al Shoyaib A, Archie SR, Karamyan VT. Intraperitoneal route of drug administration: should it be used in experimental animal studies? Pharm Res. 2020;37(1).
  39. Cashman J. Routes of administration. Clinical Pain Management Second Edition: Acute Pain, 2nd Edition. 2008. p. 201–16.
  40. Zhao Y, Yang G, Zhao Z, Wang C, Duan C, Gao L, et al. Antidepressant-like effects of Lactobacillus plantarum DP189 in a corticosterone-induced rat model of chronic stress. Behav Brain Res. 2020;395:112853.
  41. Mesripour A, Rakhshankhah P. A synbiotic mixture ameliorates depressive behavior induced by dexamethasone or water avoidance stress in a mouse model. Turkish J Pharm Sci. 2021;18(1):21–7.
  42. Li H, Wang P, Huang L, Li P, Zhang D. Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model. Neurogastroenterol Motil. 2019;31(10):1–13.
  43. Chen X, Meng S, Yu Y, Li S, Wu L, Zhang Y. The role of probiotic intervention in regulating gut microbiota, short-chain fatty acids and depression-like behavior in lead-exposed rats. Int J Occup Med Environ Health. 2022;35(1):95–106.

How to Cite

Evilia, W. ., Wahyuni, A. A. S. ., Ida Aju Kusuma Wardani, Putra, I. W. G. A. E. ., Lely Setyawati Kurniawan, Diniari, N. K. S. ., Ardani, I. G. A. I. ., & Arijana, I. G. K. N. . (2023). Effect of probiotics as adjuvant therapy of antidepressants in male Wistar rats with anhedonia behavior. Bali Medical Journal, 12(2), 1334–1341.




Search Panel

Wati Evilia
Google Scholar
BMJ Journal

Anak Ayu Sri Wahyuni
Google Scholar
BMJ Journal

Ida Aju Kusuma Wardani
Google Scholar
BMJ Journal

I Wayan Gede Artawan Eka Putra
Google Scholar
BMJ Journal

Lely Setyawati Kurniawan
Google Scholar
BMJ Journal

Ni Ketut Sri Diniari
Google Scholar
BMJ Journal

I Gusti Ayu Indah Ardani
Google Scholar
BMJ Journal

I Gusti Kamasan Nyoman Arijana
Google Scholar
BMJ Journal