NMDA receptor modulation by Esculetin: Investigating behavioral, biochemical and neurochemical effects in schizophrenic mice model.
Iqra Khalid, Uzma Saleem, Bashir Ahmad, Mohammed F Hawwal, Ramzi A Mothana
Saudi Pharmaceutical Journal April 1, 2024 DOI: 10.1016/j.jsps.2024.101994 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model study Peer reviewed |
|---|---|
| Population | Swiss albino mice |
| Interventions | Esculetin Clozapine |
| Topics | Ketamine |
| Keywords | Bdnf Esculetin Oxidative stress Schizophrenia Antipsychotic medicine Herbal treatment Phytotherapy Brain inflammation neuroinflammation Neural swelling |
| Citations | 11 |
| Key points | Esculetin significantly attenuated ketamine-induced behavioral symptoms, oxidative stress, and neuroinflammation, and increased BDNF levels in the hippocampus, cortex, and striata. |
Abstract
Schizophrenia, a global mental health disorder affecting approximately 1 % of the population, is characterized by neurotransmitter dysregulation, particularly dopamine, serotonin, and glutamate. Current antipsychotic therapies, despite their efficacy, are accompanied by adverse effects, which has motivated researchers to investigate more secure substitutes. This study examines the potential antipsychotic effects of esculetin, a natural coumarin derivative recognized for its wide-ranging pharmacological activities (anti-inflammatory, antioxidant, anti-pathogenic, anticancer, and neuroprotective), in animal model of schizophrenia induced by ketamine. In order to induce disease, acute and chronic ketamine administration was performed on Swiss albino mice, supplemented with esculetin (as the test substance) and clozapine (as the reference standard). Behavioral studies and biochemical assays were performed to evaluate positive, negative, and cognitive symptoms of schizophrenia, as well as antioxidant and oxidant levels in various brain regions. Esculetin demonstrated significant improvements in behavioral symptoms, attenuated oxidative stress and neuroinflammation, and modulated neurotransmitter levels. Afterwards, ELISA was performed to evaluate levels of schizophrenia biomarkers AChE, BDNF. Moreover, proinflammatory cytokines (IL-6 and TNF-α) and NF-κB were also determined. Histopathological parameters of under study brain parts i.e., hippocampus, cortex and striata were also assessed. Esculetin and clozapine significantly (***p < 0.0001) altered ketamine induced behavioral symptoms and attenuated ketamine induced oxidative stress and neuroinflammation. Additionally, esculetin significantly (***p < 0.0001) altered neurotransmitter (dopamine, serotonin, glutamate) levels. ELISA analysis depicts ketamine reduced BDNF levels in hippocampus, cortex and striata while esculetin significantly (***p < 0.0001) increased BDNF levels in under study three parts of brain. Histopathological changes were seen in test groups. The findings of this study indicate that esculetin may have therapeutic potential in the treatment of schizophrenia induced by ketamine. As a result, esculetin may have the potential to be utilized as a treatment for schizophrenia.
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
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology February 20, 2025
- Investigating the effects of chlorogenic acid on novel object recognition memory impairment, hyperlocomotion, and prefrontal BDNF expression in a sub-chronic ketamine-induced schizophrenia-like rat model IBRO Neuroscience Reports July 24, 2026
- AMELIORATIVE EFFECTS OF SELECTIVE PDE-10 INHIBITORS AGAINST KETAMINE-MEDIATED SCHIZOPHRENIC OUTCOMES IN MICE Asian Journal of Pharmaceutical and Clinical Research January 7, 2026
- The potential therapeutic effect of donepezil on a ketamine rat model of psychosis Journal of advanced pharmacy education and research 2025