Low Dose Lipopolysaccharide-Induced Depressive-Like Phenotype is Mediated by Proinflammatory Cytokines in Mice and Role of Ketamine
1,3, 1, 2, 1, 3
- 1Department of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, INDIA.
- 2Department of Pharmacy, College of Pharmaceutical Sciences, Dayananda Sagar University, Bangalore, Karnataka, INDIA.
- 3Department of Biology, Jubilant Biosys Ltd., Bangalore, Karnataka, INDIA.
CORRESPONDENCE
Dr. Vandurayanpet Kaliyamoorthy Kalaichelvan
Department of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram-608002, Tamil Nadu, INDIA.
Received: 25-11-2022; Accepted: 10-05-2024.
Volume 58, Issue 3s (Supplement) · pp. s777-s786 · 2024 · DOI: 10.5530/ijper.58.3s.79
ABSTRACT
Background: Depression is a common mental illness, with an estimated 3.8% of global population affected. In the pathophysiology of depression, ketamine acts quickly in patients. Treatment with low-dose ketamine upon administration to stressed C57BL/6J mice is now a major translational research area to facilitate further innovation.Objectives: The present work was aimed to establish a depressant like animal model after 6 days of LPS injection, where LPS did not promote body weight loss.Materials and Methods: Peripheral administration of low dose of Lipopolysaccharide (LPS) activates cytokines and culminate in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in the forced swim and anhedonia in sucrose preference tests. Cytokines like TNF-α, IL-6, IL-1β and IFN-γ were determined in brain homogenate and in plasma using western blot performed with automated Jess system (ProteinSimple) and ELISA respectively.Results: Ketamine prevents development of depressive-like behavior by decreasing swimming behavior and increasing preference to sucrose in stressed animals. Ketamine treatment reduced the LPS induced secretion of IFN-γ (p<0.05 for 30 mpk), IL-6 (p<0.05 for 30 mpk), TNF-α (p<0.0001 for 30 mpk) and IL-1β in plasma. Similarly, ketamine treatment reduced the LPS induced secretion of IFN-γ (p<0.001 for 10 and 30 mpk), IL-6, TNF-α (p<0.01 for 10 and 30 mpk) and IL-1β (p<0.05 for 10 mpk, p<0.0001 for 30 mpk) in brain. The plasma and brain concentrations of ketamine were analysed using LC-MS/MS and Brain/ Plasma ratio (B/P) of ketamine at 10 and 30 mpk were calculated as 0.70 and 0.82 respectively.Conclusion: In summary, these data emphasizes that ketamine treatment modulate cytokine level, showed good brain to plasma exposure and provides its anti-stress effects in the C57BL/6 mouse strain, which may be possible reason for the anti-depression property and is relevant to human stress-induced depression.
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Praharaj, S., Kalaichelvan, V. K., Murugan, V., Venkatachalam, V., & Ahmad, I. (2024). Low Dose Lipopolysaccharide-Induced Depressive-Like Phenotype is Mediated by Proinflammatory Cytokines in Mice and Role of Ketamine. Indian Journal of Pharmaceutical Education and Research, 58(3s), s777-s786. https://doi.org/10.5530/ijper.58.3s.79
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