1. Lycopene alleviates BCG-induced depressive phenotypes in mice by disrupting 5-HT3 receptor - IDO1 interplay in the brain.
- Author
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Deore R, Ansari R, Awathale SN, Shelke M, Badwaik HR, Goyal SN, and Nakhate KT
- Subjects
- Animals, Mice, Male, Phenotype, Molecular Docking Simulation, Serotonin metabolism, BCG Vaccine pharmacology, Ondansetron pharmacology, Behavior, Animal drug effects, Serotonin 5-HT3 Receptor Antagonists pharmacology, Antidepressive Agents pharmacology, Minocycline pharmacology, Lycopene pharmacology, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors, Depression drug therapy, Depression metabolism, Brain drug effects, Brain metabolism, Receptors, Serotonin, 5-HT3 metabolism
- Abstract
The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG). Lycopene (intraperitoneal; i.p.) was administered alone or in combination with 5-HT3 receptor antagonist ondansetron (i.p.) or IDO1 inhibitor minocycline (i.p.), and the behavioral screening was performed by the sucrose preference test, open field test, tail suspension test, and splash test which are based on the different principles. Further, the brains were subjected to the biochemical analysis of serotonin and its precursor tryptophan by the HPLC. The results showed depression-like behavior in BCG-inoculated mice, which was reversed by lycopene administration. Moreover, prior treatment with ondansetron or minocycline potentiated the antidepressant action of lycopene. Minocycline pretreatment also enhanced the antidepressant effect of ondansetron indicating the regulation of IDO1 activity by 5-HT3 receptor-triggered signaling. Biochemical analysis of brain samples revealed a drastic reduction in the levels of tryptophan and serotonin in depressed animals, which were restored following treatment with lycopene and its combination with ondansetron or minocycline. Taken together, the data from molecular docking, behavioral experiments, and biochemical estimation suggest that lycopene might block the 5-HT3 receptor and consequently inhibit the activity of IDO1 to ameliorate BCG-induced depression in mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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