The potential therapeutic effect of donepezil on a ketamine rat model of psychosis
K. Mehdar
Journal of advanced pharmacy education and research 2025 DOI: 10.51847/oddqdge3fy (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Adult male albino rats |
| Interventions | Donepezil Clozapine Ketamine |
| Dose | 25 mg/kg ketamine HCl |
| Duration | Ketamine for 14 days; clozapine or donepezil from days 8 to 21 |
| Measures | open field test, social interaction test, Y-Maze test, GFAP immunohistochemistry, morphometric evaluation of the hippocampus |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine produced psychosis-like behavioral symptoms and hippocampal degeneration in rats, including increased GFAP expression. Both donepezil and clozapine reduced these degenerative and behavioral changes. The authors suggest donepezil may potentially substitute for clozapine in treating ketamine-induced psychosis. |
Abstract
Mental illnesses like bipolar disorder and schizophrenia often present psychotic symptoms. Current antipsychotic medications, including clozapine, can cause serious side effects. This study investigates the potential therapeutic effects of the cholinesterase inhibitor donepezil compared to clozapine in a ketamine-induced psychosis model in rats. Forty adult male albino rats were divided into four groups: a control group, a psychosis group (given 25 mg/kg ketamine HCl for 14 days), a Clozapine + Psychosis group (received clozapine from days 8 to 21), and a Donepezil + Psychosis group (received donepezil during the same period). Neurobehavioral changes were assessed using the open field test, social interaction test, and Y-Maze test. After the study, the rats were euthanized for histological analysis, including GFAP immunohistochemistry and morphometric evaluation of the hippocampus. Ketamine induced positive, negative, and cognitive symptoms of psychosis and caused hippocampal degeneration, evident through cellular changes and increased GFAP expression. Both donepezil and clozapine mitigated these degenerative and behavioral symptoms associated with psychosis. The administration of ketamine resulted in psychotic symptoms and hippocampal degeneration in rats. Both clozapine and donepezil improved these outcomes, suggesting that donepezil may potentially substitute clozapine in treating ketamine-induced psychosis, addressing both clinical and histological issues effectively.
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
Cites 7
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways Journal of Psychopharmacology September 17, 2013
- Long-Lasting Antidepressant Action of Ketamine, but Not Glycogen Synthase Kinase-3 Inhibitor SB216763, in the Chronic Mild Stress Model of Mice PLoS One February 4, 2013
- A review of potential neuropathological changes associated with ketamine Expert Opinion on Drug Safety May 3, 2022
- NMDA receptor modulation by Esculetin: Investigating behavioral, biochemical and neurochemical effects in schizophrenic mice model. Saudi Pharmaceutical Journal April 1, 2024
and 2 more in the library