Psychosis: The Utility of Ketamine as a Pharmacological Model of Psychotic-like Symptoms in Rodents: A Review of Dosage Regimens
Biology January 25, 2026 Claire A. Rice, Robert W. Stackman
Ketamine administration protocols vary widely and are used to model psychotic-like behavior in rodents. This review compares classic and contemporary studies using different dosing regimens, focusing on behavioral tasks and analytical methods that validate psychosis-like and schizophrenia-like symptoms. Acute ketamine protocols are best suited for addiction research or as a preliminary step before longer studies. Repeated, sub-chronic, or chronic administration yields more comprehensive models of psychosis-like behavior and is better for examining enduring cognitive and neurobiological impairments. Intravenous or intraperitoneal administration at frequent intervals or as a bolus may sustain higher bioavailable ketamine levels, producing a more robust psychosis-like phenotype relevant for studying long-term cognitive and neurological dysfunction.