The objective of the present study was to evaluate the influence of Loxoprofen on serotonin, noradrenaline and dopamine levels in absence or presence of Lipopolysaccharide (LPS) after chronic mild stress treatment in mice brain. Background: It has been reported that there is an abnormal prostaglandin levels in depression. Several studies indicated that there has been an elevated level of prostaglandins in depression. It has been reported that Loxoprofen remarkably decrease the PGE2 level in regions of brain. Method: There was an estimation of serotonin, noradrenaline and dopamine levels in mice brain after 21 days of chronic mild stress schedule in which mice were subjected to treatment of Loxoprofen (16.8mg/kg, p.o.) or Venlafexine (4mg/kg, i.p.) with or without treatment of LPS (0.5mg/kg, i.p.) for last 14 days. Results: There was a significant decrease in brain serotonin, noradrenaline and dopamine levels in stressed mice as compared to normal mice. There was a significant decrease in brain serotonin, noradrenaline and dopamine levels in LPS treated stressed mice as compared to LPS treated normal mice. The treatment of Loxoprofen in LPS treated stressed mice showed a significant increase in brain serotonin and noradrenaline levels but not dopamine levels as compared to LPS treated stressed mice. The treatment of Venlafexine in LPS treated stressed mice showed a significant increase in all above mentioned three brain neurotransmitters levels as compared to LPS treated stressed mice.Conclusion: The results of the present study showed that Loxoprofen influence the LPS induced alterations in serotonin and noradrenaline levels in mice brain after 21 day exposure of chronic mild stress schedule. It can indicate the possible antidepressant-like effect of Loxoprofen in mice subjected to chronic mild stress schedule, having its possible implication in future treatment of depression.
Cite this article:
Kundu Smita S, Digvijaysinh G. Rana. Possible Influence of Loxoprofen in Lipopolysaccharide Induced Alterations in Brain Serotonin, Noradrenaline and Dopamine Levels in Chronic Mild Stress Treated Mice. Research Journal of Pharmacy and Technology. 2022; 15(5):2081-6. doi: 10.52711/0974-360X.2022.00344
Kundu Smita S, Digvijaysinh G. Rana. Possible Influence of Loxoprofen in Lipopolysaccharide Induced Alterations in Brain Serotonin, Noradrenaline and Dopamine Levels in Chronic Mild Stress Treated Mice. Research Journal of Pharmacy and Technology. 2022; 15(5):2081-6. doi: 10.52711/0974-360X.2022.00344 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-5-26
1. Sharma I, Kaur M, Parashar B, Kainth A. Depression: An overview. Asian Journal of Research in Pharmaceutical Sciences. 2014; 4(1): 28-31.
2. Dave PH, Vishnupriya V, Gayathri R. Herbal remedies for anxiety and depression - A review. Research Journal of Pharmacy and Technology. 2016; 9(8):1253-6. doi.org/10.5958/0974-360X.2016.00237.7
3. Uppala P, Murali KB, Atchuta K, Ramji V. Experimental evaluation of antidepressant activity of aqueous and methanolic leaf and shoot extracts of Ageratum conyzoides Linn in Mice. Asian Journal of Pharmaceutical Research. 2016; 6(3): 153-8. doi.org/10.5958/2231-5691.2016.00022.8
4. Uppala P, Atchuta K, Kumar, Patro S, Murali KB. Experimental evaluation of antidepressant activity of aqueous and chloroform leaf and shoot extracts of Eicchornia crassipes Linn in Mice. Asian Journal Research in Pharmaceutical Sciences. 2015; 5(3): 139-44.
5. Malarkodi V, Ravichandiran V, Ramamoorthy S, Vijayalakshmi A, Srikanth J. Antidepressant-Like Effects of the ethanolic extract of Albizzia lebbeck (Linn) leaves in animal models of depression. Research Journal of Pharmacognosy and Phytochemistry. 2010; 2(1): 30-3.
6. Shewale A, Naikwade NS, Ladda PL. Antidepressant activity of Chrysanthemum morifolium Linn in mice. Asian Journal of Research in Pharmaceutical Sciences. 2019; 9(4):260-66. doi.org/10.5958/2231-5659.2019.00040.7
7. Adnaik RS, Gavarkar PS, Mohite SK, Magdum CS. Anti-depressant activity of ethanolic extract of Citrullus vulgaris seeds in experimentally induced depressed mice. Research Journal of Pharmacy and Technology. 2014; 7(6): 660-2.
8. Zajecka JM. Clinical issues in long-term treatment with antidepressants. Journal of Clinical Psychiatry. 2000; 61: 20-5.
9. Patel MA, Patel CM, Patel DB, Anand IS, Patel CN. A review on novel strategies for pharmacotherapy of depression. Research Journal of Pharmacology and Pharmacodynamics. 2010; 2(2):153-9.
10. Patel A. The role of inflammation in depression. Psychiatria Danubina. 2013; 25: S216-S223.
11. Farooq RK, Asghar K, Kanwal S and Zulqernain A. Role of inflammatory cytokines in depression: Focus on interleukin-1β. Biomedical Reports. 2017; 6: 15-20. doi.org/ 10.3892/br.2016.807
12. Felger JC and Lotrich FE. Inflammatory cytokines in depression: Neurobiological mechanisms and therapeutic implication. Journal of Neuroscience. 2013; 29; 199-229. doi.org/10.1016/j.neuroscience.2013.04.060
13. Jangpangi D. Depression and inflammation: Pathophysiology and therapeutic implications. CHRISMED Journal of Health Research. 2016; 3: 155-60. doi.org/10.4103/2348-3334.183728
14. Noto C, Rizzo LB, Mansur RB, McIntyre RS, Maes M and Brietzke E. Targeting the inflammatory pathway as a therapeutic tool for major depression. Neuroimmunomodulation. 2014; 21: 131-39. doi.org/10.1159/000356549
15. Deepak Kumar. Comorbid depression in inflammatory bowel disease. Asian Journal of Research in Pharmaceutical Sciences. 2020; 10(1):35-8. doi.org/10.5958/2231-5659.2020.00008.9
16. Lieb J, Karmali R and Horrobin DF. Elevated levels of PGE2, and the thromboxane B2 in depression. Prostaglandins Leukotrienes and Medicine. 1983; 10(4); 361-67. doi.org/ 10.1016/0262-1746(83)90048-3
17. Calabrese JR, Skwerer RG, Barna B, Gulledge AD, Valenzuela R, Butkus A et al. Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Research. 1986; 17(1): 41-7. doi.org/10.1016/0165-1781(86)90040-5
18. Linnoila M, Whorton AR, Rubinow DR, Cowdry RW, Ninan PT and Waters RM. CSF prostaglandin levels in depressed and schizophrenic patients. Archives of General Psychiatry. 1983; 40: 405-06. doi.org/10.1001/archpsyc.1983.01790040059008
19. Fritz M, Klawonn AM, Nilsson A, Singh AK, Lazarus M, Löfberg A et al. Prostaglandin dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice. Journal of Clinical Investigation. 2016; 126(2): 695-705. doi.org/10.1172/JCI83844
20. Brenneis C, Coste O, Altenrath K, Angioni C, Schmidt H, Schuh CD et al. Anti-inflammatory role of microsomal prostaglandin E synthase-1 in a model of neuroinflammation. Journal of Biological Chemistry. 2010; 286(3): 2331-42. doi.org/10.1074/jbc.M110.157362
21. Ohishi K, Ueno R, Nishino S, Sakai T and Hayaishi O. Increased level of salivary prostaglandins in patients with major depression. Biological Psychiatry. 1988; 23(4): 326-34. doi.org/10.1016/0006-3223(88)90283-1
22. Nishino S, Ueno R, Ohishi K, Sakai T and Hayaishi O. Salivary prostaglandin concentrations: possible state indicators for major depression. American Journal of Psychiatry. 1989; 146(3): 365-68. doi.org/10.1176/ajp.146.3.365
23. De Paiva VN, Lima SN, Fernandes MM, Soncini R, Andrade CA and Giusti-Paiva A. Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice. Behaviour Brain Research. 2010; 215: 146-51. doi.org/10.1016/j.bbr.2010.07.015
24. Li RC, Row BW, Gozal E, Kheirandish L, Fan Q, Brittian KR et al. Cyclooxygenase 2 and intermittent hypoxia-induced spatial deficits in the rat. American Journal Respiratory and Critical Care Medicine. 2003; 168(4): 469-75. doi.org/10.1164/rccm.200211-1264OC
25. Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Müller B et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double- blind, randomized, placebo controlled, add on pilot study to reboxetine. Molecular Psychiatry. 2006; 11: 680-84. doi.org/10.1038/sj.mp.4001805
26. Teeling JL, Cunningham C, Newman TA and Perry VH. The effect of non-steroidal anti- inflammatory agents on behavioural changes and cytokine production following systemic inflammation: implications for a role of COX-1. Brain Behaviour and Immunity. 2010; 24: 409-19. doi.org/10.1016/j.bbi.2009.11.006
27. Lee RE. The influence of psychotropic drugs on prostaglandin biosynthesis. Prostaglandins. 1974; 5: 63-8. doi.org/10.1016/s0090-6980(74)80132-2
28. Bekemeier H, Giessler AJ and Vogel E. Influence of MAO inhibitors, neuroleptics, morphine, mescaline, divascan, aconitine, and pyrogenes on prostaglandin biosynthesis. Pharmacological Research Communication. 1977; 9: 587-98. doi.org/10.1016/s0031-6989(77)80087-8
29. Fjalland B. Influence of various substances on prostaglandin biosynthesis by guinea pig chopped lung. Journal of Pharmacy and Pharmacology. 1976; 28: 683. doi.org/10.1111/j.2042-7158.1976.tb02836.x
30. Hong SL, Carty T and Deykin D. Tranylcypromine and 15-hydroperoxy arachidonate affect arachidonic acid release in addition to inhibition of prostaglandin synthesis in calf aortic endothelial cells. Journal of Biological Chemistry. 1980; 255: 9538-40. doi.org/10.1016/S0021-9258(18)43423-0
31. Mtabaji JP, Manku MS and Horrobin DF. Actions of the tricyclic anti-depressant clomipramine on responses to pressor agents. Interactions with prostaglandin E2. Prostaglandins. 1977; 14: 273-81. doi.org/10.1016/0090-6980(77)90161-7
32. Futaki N, Harada M, Sugimoto M, Hashimoto Y, Honma Y, Arai I et al. The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammation. Journal of Pharmacy and Pharmacology. 2009; 61: 607-14. doi.org/10.1211/jpp/61.05.0009
33. Thomas J, Khanam R and Vohora D. Augmentation of effect of venlafaxine by folic acid in behavioral paradigms of depression in mice: evidence of serotonergic and pro-inflammatory cytokine pathways. Pharmacological Reports. 2016; 68(2): 396-403. doi.org/10.1016/j.pharep.2015.10.003
34. Mello BS, Monte AS, McIntyre RS, Soczynska JK, Custódio CS, Cordeiro RC et al. Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration. Journal of Psychiatry Research. 2013; 47(10): 1521-29. doi.org/10.1016/j.jpsychires.2013.06.008
35. Chen Y, Wang HD, Xia X, Kung HF, Pan Y and Kong LD. Behavioural and biochemical studies of total furocoumarins from seeds of Psoraleacorylifolia in the chronic mild stress model of depression in mice. Phytomedicine. 2007; 14: 523-29. doi.org/10.1016/j.phymed.2006.09.007
36. Jacobowitz DM and Richardson SJ. Method for the rapid determination of norepinephrine, dopamine, and serotonin in the same brain region. Pharmacology Biochemistry and Behavior.1977; 8: 515-19. doi.org/10.1016/0091-3057(78)90380-5
37. Bartolomucci A and Leopardi R. Stress and Depression: Preclinical Research and Clinical Implications. PLoS One. 2009; 4(1): e4265. doi.org/10.1371/journal.pone.0004265
38. Park SY, Kim KB, Ahn SH, Kim HH. Anti-depressive effects of Gami-Shinkiwhanin immobilization stressed aging mice. Research Journal of Pharmacy and Technology. 2018; 11(5):1909-16. doi.org/10.5958/0974-360X.2018.00354.2