Vitamin B6 Antidepressant Effects Are Comparable to Common Antidepressant Drugs in Bacillus-Calmette-Guerin Induced Depression Model in Mice
Objective: Bacillus-Calmette-Guerin (BCG) inoculation in mice produces an acute period of illness followed by a chronic depressive-like behavior period that lasts for few weeks. The aim was to evaluate vitamin B6 antidepressant effect in comparison with common antidepressants.
Method: BCG (0.2 ml/mouse) single dose was intraperitoneally inoculated in male mice. Vitamin B6 (100 mg/kg), fluoxetine, imipramine, or venlafaxine (10 mg/kg each) were intraperitoneally injected for 14 consecutive days following BCG administration. Illness was evaluated following inoculation and depressive-like behaviors were assessed on days 7 and 14.
Results: Illness was induced by BCG since mice lost weight and locomotor activity was reduced. Illness was prevented by vitamin B6 similar to antidepressant drugs. Despair was measured by immobility time during the forced swim test and BCG increased it compared to control (193 ± 3s vs 151 ± 7s, P < 0.01) on day 7, and (200 ± 5s vs 147 ± 6s, P < 0.001) on day 14. Vitamin B6, like antidepressants, reduced despair. BCG clearly induced anhedonia evaluated by sucrose preference test (47.5%), and it was soothed by B6 and the antidepressants. Novelty-suppressed feeding test evaluated long term depressive behavior after 14 days. BCG increased the latency to first feeding (222 ± 41s vs control 87 ± 2.6s, P < 0.001) and reduced food consumption per body weight (13 ± 1 mg/g vs control 19 ± 2 mg/g, P < 0.001) while B6 like antidepressants reduced latency and improved food consumption.
Conclusion: Vitamin B6 efficiently prevented BCG sickness and depression that was comparable to common antidepressant drugs. Therefore, B6 supplement for preventing depression in high-risk individuals is suggested for further clinical research.
2. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008;29(3):287-91.
3. Anacker C, Zunszain PA, Carvalho LA, Pariante CM. The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology. 2011;36(3):415-25.
4. Zheng YQ, Naguib YW, Dong Y, Shi YC, Bou S, Cui Z. Applications of bacillus Calmette-Guerin and recombinant bacillus Calmette-Guerin in vaccine development and tumor immunotherapy. Expert Rev Vaccines. 2015;14(9):1255-75.
5. Rana P, Sharma AK, Jain S, Deshmukh P, Bhattacharya SK, Banerjee BD, et al. Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice. J Basic Clin Physiol Pharmacol. 2016;27(6):569-76.
6. Saleh LA, Hamza M, El Gayar NH, Abd El-Samad AA, Nasr EA, Masoud SI. Ibuprofen suppresses depressive like behavior induced by BCG inoculation in mice: role of nitric oxide and prostaglandin. Pharmacol Biochem Behav. 2014;125:29-39.
7. Moreau M, André C, O'Connor JC, Dumich SA, Woods JA, Kelley KW, et al. Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior. Brain Behav Immun. 2008;22(7):1087-95.
8. Herbison CE, Hickling S, Allen KL, O'Sullivan TA, Robinson M, Bremner AP, et al. Low intake of B-vitamins is associated with poor adolescent mental health and behaviour. Prev Med. 2012;55(6):634-8.
9. Shaik MM, Gan SH. Vitamin supplementation as possible prophylactic treatment against migraine with aura and menstrual migraine. Biomed Res Int. 2015;2015:469529.
10. Allen GF, Neergheen V, Oppenheim M, Fitzgerald JC, Footitt E, Hyland K, et al. Pyridoxal 5'-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic L-amino acid decarboxylase and vitamin B(6) deficiency states. J Neurochem. 2010;114(1):87-96.
11. Hvas AM, Juul S, Bech P, Nexø E. Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom. 2004;73(6):340-3.
12. Skarupski KA, Tangney C, Li H, Ouyang B, Evans DA, Morris MC. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Am J Clin Nutr. 2010;92(2):330-5.
13. Mesripour A, Hajhashemi V, Kuchak A. Effect of concomitant administration of three different antidepressants with vitamin B6 on depression and obsessive compulsive disorder in mice models. Res Pharm Sci. 2017;12(1):46-52.
14. Bueno-Notivol J, Gracia-García P, Olaya B, Lasheras I, López-Antón R, Santabárbara J. Prevalence of depression during the COVID-19 outbreak: A meta-analysis of community-based studies. Int J Clin Health Psychol. 2021;21(1):100196.
15. Hu S, Tucker L, Wu C, Yang L. Beneficial Effects of Exercise on Depression and Anxiety During the Covid-19 Pandemic: A Narrative Review. Front Psychiatry. 2020;11:587557.
16. Gharaati Sotoudeh H, Alavi SS, Akbari Z, Jannatifard F, Artounian V. The Effect of Brief Crisis Intervention Package on Improving Quality of Life and Mental Health in Patients with COVID-19. Iran J Psychiatry. 2020;15(3):205-12.
17. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. Jama. 2010;303(1):47-53.
18. Mesripour A, Alhimma F, Hajhashemi V. The effect of vitamin B6 on dexamethasone-induced depression in mice model of despair. Nutr Neurosci. 2019;22(10):744-9.
19. Dulawa SC, Holick KA, Gundersen B, Hen R. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology. 2004;29(7):1321-30.
20. Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci. 2002;23(5):238-45.
21. Strekalova T, Gorenkova N, Schunk E, Dolgov O, Bartsch D. Selective effects of citalopram in a mouse model of stress-induced anhedonia with a control for chronic stress. Behav Pharmacol. 2006;17(3):271-87.
22. Dantzer R. Cytokine, sickness behavior, and depression. Neurol Clin. 2006;24(3):441-60.
23. Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am. 2009;29(2):247-64.
24. Vijaya Kumar K, Rudra A, Sreedhara MV, Siva Subramani T, Prasad DS, Das ML, et al. Bacillus Calmette-Guérin vaccine induces a selective serotonin reuptake inhibitor (SSRI)-resistant depression like phenotype in mice. Brain Behav Immun. 2014;42:204-11.
25. Yan S, You ZL, Zhao QY, Peng C, He G, Gou XJ, et al. Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model. Kaohsiung J Med Sci. 2015;31(12):605-12.
26. Mesripour A, Sajadian S, Hajhashemi V. Antidepressant-like effect of vitamin B6 in mice forced swimming test and the possible involvement of the noradrenergic system. J Rep Pharma Sci. 2019; 8(2):133-8.
27. Zahiu CD, Rimbas M. Neuropsychiatric side-effects of interferon-alpha treatment: pathophysiology and therapeutic options. Maedica (Bucur). 2014;9(2):121-6.
28. Planchez B, Surget A, Belzung C. Animal models of major depression: drawbacks and challenges. J Neural Transm (Vienna). 2019;126(11):1383-408.
29. Dulawa SC, Hen R. Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test. Neurosci Biobehav Rev. 2005;29(4-5):771-83.
30. Surget A, Saxe M, Leman S, Ibarguen-Vargas Y, Chalon S, Griebel G, et al. Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal. Biol Psychiatry. 2008;64(4):293-301.
31. Iijima M, Fukumoto K, Chaki S. Acute and sustained effects of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test. Behav Brain Res. 2012;235(2):287-92.
|Issue||Vol 17 No 2 (2022)|
|Antidepressive Agents Anhedonia Animal Experimentation BCG Vaccine Depression Vitamin B6|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|