Niacin mitigates blood-brain barrier tight junctional proteins dysregulation and cerebral inflammation in ketamine rat model of psychosis: Role of GPR109A receptor.
Weam W Ibrahim, R. H. Sayed, Esraa A Kandil, W. Wadie
Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2022 DOI: 10.1016/j.pnpbp.2022.110583 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Interventions | Ketamine Niacin Mepenzolate bromide (MPN) |
| Dose | Ketamine 30 mg/kg/day i.p.; niacin 40 mg/kg/day p.o.; MPN 5 mg/kg/day i.p. |
| Duration | Ketamine for 5 consecutive days, then niacin with or without MPN for 15 days; behavioral testing 3 days before the end |
| Measures | Open field test, novel object recognition test, social interaction test, forced swimming test |
| Topics | Esketamine Ketamine |
| Key findings | Niacin ameliorated ketamine-induced behavioral deficits and restored hippocampal blood-brain barrier integrity in rats, reducing TNF-α and MMP-9, increasing netrin-1, and raising ZO-1, occludin, and claudin-5 expression. Because the GPR109A blocker mepenzolate bromide partially abolished these effects, the authors conclude that GPR109A signaling partially mediates niacin's antipsychotic-like effects and may be a therapeutic target. |
Abstract
Dysregulated inflammatory responses and blood-brain barrier (BBB) dysfunction are recognized as central factors in the development of psychiatric disorders. The present study was designed to evaluate the effect of niacin on BBB integrity in ketamine-induced model of psychosis. Meanwhile, mepenzolate bromide (MPN), a GPR109A receptor blocker, was used to investigate the role of this receptor on the observed niacin's effect. Male Wistar rats received ketamine (30 mg/kg/day, i.p) for 5 consecutive days and then niacin (40 mg/kg/day, p.o), with or without MPN (5 mg/kg/day, i.p), was given for the subsequent 15 days. Three days before the end of experiment, rats were behaviorally tested using open field, novel object recognition, social interaction, and forced swimming tests. Niacin significantly ameliorated ketamine-induced behavioral deficits, amended gamma aminobutyric acid and glutamate concentration, decreased tumor necrosis factor-α and matrix metallopeptidase 9 levels, and increased netrin-1 contents in the hippocampus of rats. Niacin also augmented the hippocampal expression of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the BBB integrity. Moreover, the histopathologic changes in hippocampal neurons were alleviated. Since all the beneficial effects of niacin in the present investigation were partially abolished by the co-administration of MPN; GPR109A receptor was proven to partially mediate the observed antipsychotic effects of niacin. These data revealed that GPR109A-mediated signaling pathways might represent potential targets for therapeutic interventions to prevent or slow the progression of psychosis.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia. Journal of Neuroimmune Pharmacology July 3, 2025
- Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia. Journal of Neuroimmune Pharmacology July 25, 2025
- Esketamine relieves depressive-like behaviors in MPTP-induced Parkinson disease mice via GPR109A-dependent reduction of neuroinflammation Brain Research Bulletin October 27, 2025
- Baricitinib ameliorates behavioral deficits and NLRP3-related neuroinflammation in a ketamine rat model of schizophrenia: Role of JAK2/STAT3 and PI3K/AKT/mTOR signaling. International Immunopharmacology August 19, 2026
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