Psychosis: The Utility of Ketamine as a Pharmacological Model of Psychotic-like Symptoms in Rodents: A Review of Dosage Regimens

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.