EFFECT OF DRUGS MODULATING SEROTONERGIC SYSTEM ON THE ANTI-DEPRESSANT ACTION OF FLUOXETINE AND DESIPRAMINE IN ALBINO MICE
Main Article Content
Keywords
Fluoxetine, desipramine, depression, tail suspension test, chronic mild stress test
Abstract
Introduction:
Depression is a complex and prevalent psychiatric disorder that necessitates a thorough understanding of its underlying mechanisms to develop more effective treatment strategies. This study investigated the effect of drugs modulating the serotonergic system on the antidepressant action of fluoxetine and desipramine in albino mice.
Material & Methods:
The two widely used behavioural tests, the tail suspension test and the chronic mild stress test, were employed to evaluate the antidepressant potential of these drugs.Six albino mice were included in each experimental group.
Result & discussion:
The results of this study revealed a noteworthy finding regarding the impact of ondansetron, a serotonin antagonist, on the antidepressant capabilities of fluoxetine and desipramine. Contrary to expectations, it was observed that ondansetron did not impair the antidepressant effects of either fluoxetine or desipramine. Instead, a surprising potentiation of their antidepressant actions was noted in the presence of ondansetron.
Conclusion:
These findings suggest that the serotonergic system, often implicated in the pathophysiology of depression, may have a more intricate role in antidepressant response than previously understood. Further research is warranted to elucidate the mechanisms underlying this unexpected interaction between serotonergic modulators and established antidepressants. Such insights may contribute to the development of novel therapeutic approaches for the treatment of depression, ultimately improving the lives of individuals suffering from this debilitating condition.
References
2. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annual Review of Public Health. 2013;34:119-138.
3. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34(1):13-25.
4. Albert PR, Benkelfat C. The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philosophical Transactions of the Royal Society B: Biological Sciences. 2013;368(1615):20120536.
5. Belmaker RH, Agam G. Major depressive disorder.New England Journal of Medicine. 2008;358(1):55-68.
6. Krishnan V, Nestler EJ. Linking molecules to mood: new insight into the biology of depression. The American Journal of Psychiatry. 2010;167(11):1305-1320.
7. Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. Journal of Clinical Psychiatry. 2008;69 Suppl E1:4-7.
8. Wong DT, Bymaster FP, Engleman EA. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: Twenty years since its first publication. Life Sciences. 1995;57(5):411-441.
9. Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S. A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Primary Care Companion to The Journal of Clinical Psychiatry. 2004;6(4):159-166.
10. Kranzler HR, Feinn R, Morris P, Hartwell EE. A meta-analysis of the efficacy of ondansetron in the treatment of alcohol use disorder.Journal of Clinical Psychopharmacology. 2019;39(6):592-596.
11. Czachowski CL, Samson HH, Denning CE. Independent ethanol-and sucrose-maintained responding on a multiple schedule of reinforcement. Alcoholism: Clinical and Experimental Research. 1999;23(6):943-950.
12. Khanna JM, Kalant H, Shah G. Serotonin antagonists and voluntary ethanol consumption by rats. Psychopharmacology. 1980;71(1):29-33.
13. Cryan JF, Holmes A. The ascent of mouse: advances in modelling human depression and anxiety. Nature Reviews Drug Discovery. 2005;4(9):775-790.
14. Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nature Neuroscience. 2010;13(10):1161-1169.
15. Belzung C, Lemoine M. Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biology of Mood & Anxiety Disorders. 2011;1(1):9.
16. Can A, Dao DT, Terrillion CE, Piantadosi SC, Bhat S, Gould TD. The tail suspension test. J Vis Exp. 2012 Jan 28;(59):e3769. doi: 10.3791/3769
17. Willner P. The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiol Stress. 2016;6:78-93.
18. Dhawale T, Kumar S, S D. Evaluation of analgesic and anti-inflammatory activity of ibuprofen and duloxetine in animal models. Natl J Physiol Pharm Pharmacol. 2019; 9(9): 842-846.
19. Albert PR, Benkelfat C, Descarries L. The neurobiology of depression--revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos Trans R Soc Lond B Biol Sci. 2012 Sep 5;367(1601):2378-81.
20. Marazziti D. Depression and serotonin: a never-ending story. Curr Drug Targets. 2013 May 1;14(5):513.
21. Kumar S, Singh H, Sharma J. Effect of lamotrigine, levetiracetam and phenytoin on learning and memory in albino rats. Int J Med and Dent Sci 2014; 3(2):388-395
22. Johnson BA, Ait-Daoud N, Ma JZ, Wang Y. Ondansetron reduces mood disturbance among biologically predisposed, alcohol-dependent individuals. Alcohol Clin Exp Res. 2003;27(11):1773-1779.
23. Wallace A, Pehrson AL, Sánchez C, Morilak DA. Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats. Int J Neuropsychopharmacology. 2014;17(10):1695-1706.
24. Gupta D, Radhakrishnan M, Kurhe Y. Ondansetron, a 5HT3 receptor antagonist reverses depression and anxiety-like behaviour in streptozotocin-induced diabetic mice: possible implication of serotonergic system. Eur J Pharmacol. 2014;744:59-66. doi:10.1016/j.ejphar.2014.09.041
25. Luscombe GP, Martin KF, Hutchins LJ, Gosden J, Heal DJ. Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors. Br J Pharmacol. 1993;108(3):669-677.
26. Castrén E, Rantamäki T. The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity. Dev Neurobiol. 2010;70(5):289-297.
27. Berney A, Nishikawa M, Benkelfat C. The use of the selective serotonin reuptake inhibitor citalopram in the treatment of generalized social phobia. J Clin Psychopharmacol. 2008;28(4):545-547.
28. Lacasse JR, Leo J. Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS Med. 2005;2(12):e392.
29. Blier P, Ward NM. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry. 2003;53(3):193-203.
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Dr. Subir Kumar
Associate Professor, Department of Pharmacology, Phulo Jhano Medical College, Dumka.
Dr. Biswadeep Banerjee
Medical Officer (Jharkhand gov), Mohanpur, Deoghar
Dr. Akash Chandra
Assistant Professor, Department of Pharmacology, Shahid Nirmal Mahato Medical College, Dhanbad
Dr. Tanmoy Gangopadhyay
Associate Professor, Department of Pharmacology, Medical College Kolkata
Dr. Vijay Kumar
Professor, Department of Community Medicine, Laxmi Chandravansi Medical College and Hospital, Palamu
Dr. Manpreet Saini
Associate Professor, Department of Biochemistry, Laxmi Chandravansi Medical College and Hospital, Palamu