Psychosis: The Utility of Ketamine as a Pharmacological Model of Psychotic-like Symptoms in Rodents: A Review of Dosage Regimens
Claire A. Rice, Robert W. Stackman
Biology January 25, 2026 DOI: 10.3390/biology15030222 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Laboratory rodents |
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | Acute ketamine protocols suit addiction research, while repeated, sub-chronic, or chronic administration yields more comprehensive models of psychosis-like behavior and associated cognitive and neurobiological impairments. |
Abstract
Ketamine (KET) administration protocols vary widely in their design, with acute, sub-chronic, and chronic dosing regimens used to induce psychotic-like behavior in rodent models. This review compares representative classic and contemporary studies employing differing KET administration protocols to model psychosis in laboratory rodents. Specifically, we have focused on the behavioral tasks and analytical methods used to validate KET-induced symptoms of psychosis-like and schizophrenia-like behaviors. While variability in behavioral tasks complicates direct comparisons across studies, these findings provide a framework for selecting dosing strategies aligned with specific research objectives. Acute KET protocols are particularly suited for addiction research or as a preliminary approach preceding longer-term studies. In contrast, protocols utilizing repeated or sub-chronic, or chronic administration of KET tend to yield more comprehensive models of psychosis-like behavior and are better suited for examining the associated enduring cognitive and neurobiological impairments. Administering KET intravenously or intraperitoneally at frequent intervals or with a bolus dose, may sustain higher levels of bioavailable KET, thereby producing a more robust and reliable psychosis-like phenotype, especially relevant for investigations of long-term cognitive and neurological dysfunction.
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 2
- S-propargyl-L-cysteine attenuates ketamine induced schizophrenia-like behaviors and neuroinflammation in mice via inhibition of NF-κB/NLRP3 inflammasome-mediated pyroptosis. International Immunopharmacology September 22, 2026
- Chlorogenic Acid Attenuates Schizophrenia-Like Behavioral Deficits and Neuroinflammation in a Ketamine-Induced Mouse Model
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