Repeated Sub-anaesthetic dose of Ketamine Elevates Superoxide Dismutase in Pharmacological Model of Schizophrenia-Like Phenotypes in Mice

Repeated sub-anaesthetic doses of ketamine (20 mg/kg) given to mice for 14 days increased movement and rearing in a locomotor activity test and prolonged the time to enter open arms in a cognitive test, compared to a vehicle control. Ketamine also elevated superoxide dismutase (SOD) activity in brain tissue. Pretreatment with risperidone (0.5 mg/kg) from days 8–14 appeared to reduce these effects. The results suggest that repeated ketamine may alter the endogenous antioxidant system, raising SOD activity as a possible compensatory mechanism in a rodent model of schizophrenia.

Study at a glance

Abstract

Abstract Objective The study evaluated behavioural phenotypes and the level of Superioxde Dismutase activity in repeated sub-anaesthetic dose of ketamine administered to model schizophrenia in animal study. Method Animals were divided into groups (n=6), control group received distilled water (10mL/kg) as vehicle (VEH), Ketamine treated group (KET) received sub-anaesthetic dose of ketamine (20mg/kg) for 14 days consecutively. Animals in risperidone treated group (KET+RISP) were pre-treated with sub-anaesthetic dose of ketamine (20mg/kg) alone for 7 consecutive days, and from day 8-14, risperidone (0.5mg/kg) was administered 1 hour post-ketamine treatment. All treatment were administered intraperitoneally (i.p). Twenty-four (24) hours after the last treatment, Behavioural phenotypes (locomotor activity and cognition) were assessed in locomotor activity cage and elevated maze plus. Thereafter level of superioxde dismutase (SOD) activity was evaluated in homogenized brain tissue of each mouse using spectrophotometric analysis. Result KET group showed significant (p<0.05) increase in movement counts and number of rearing events in locomotor activity test, also prolonged latency to enter the open arms in cognitive assessment compared to animals that received distilled water (10mg/kg), and risperidone (0.5mg/kg) treatment. The level of Superioxide Dismutase (SOD) activity was significantly elevated in KET group compare with vehicle control and risperidone treated animals. Conclusion Repeated dose of ketamine may pose differential effect on endogenous antioxidant system which may elevate superioxide dismutase activity in ketamine induced schizophrenic rodent as positive control mechanism.