Repeated ketamine doses elevate superoxide dismutase activity in a pharmacological model of schizophrenia-like phenotypes in mice

In mice, repeated sub-anesthetic doses of ketamine (20 mg/kg for 14 days) increased movement counts and rearing in a locomotor activity test and prolonged the time to enter the open arms of an elevated plus maze, indicating heightened anxiety-like behavior. Superoxide dismutase (SOD) enzymatic activity in brain tissue was significantly elevated in ketamine-treated mice compared to controls and to mice that later received risperidone (0.5 mg/kg) from days 8 to 14. The elevated SOD activity may represent a compensatory response to oxidative stress from repeated ketamine. Risperidone appeared to prevent both the behavioral changes and the rise in SOD activity.

Study at a glance

Abstract

This study evaluated behavioral phenotypes and superoxide dismutase (SOD) enzymatic activity in a repeated sub-anesthetic dose of ketamine (KET) administered to model schizophrenia in an animal study. The animals were divided into three (3) experimental groups. The KET alone group received sub-anesthetic dose of KET (20 mg/kg) for 14 consecutive days. The control group vehicle (VEH) received distilled water (10 mL/kg) as a VEH, while the KET and risperidone (RISP) group (KET + RISP) received a sub-anesthetic dose of KET (20 mg/kg) alone for 7 consecutive days, followed by RISP (0.5 mg/kg) administered 1-h post-KET treatment from days 8 to 14. All treatments were administered intraperitoneally (i.p.). Twenty-four hours after the last treatment, behavioral phenotypes (locomotor activity and cognition) were assessed using the locomotor activity cage and the elevated plus maze (EPM). Thereafter, SOD enzymatic activity was evaluated in homogenized brain tissue from each mouse using spectrophotometric analysis. Animals that received KET (20 mg/kg i.p) alone showed a significant (P < 0.05) increase in movement counts and rearing events in the locomotor activity test. It also prolonged the latency to enter the open arms during the anxiety-induced cognitive assessment in the EPM, compared to animals that received distilled water or those that received KET and RISP. SOD enzymatic activity was significantly elevated in the KET group compared to the VEH and KET + RISP groups. The elevated SOD enzymatic activity may represent a compensatory response to the oxidative stress induced by repeated sub-anesthetic doses of KET.