INVESTIGATION OF NEUROPROTECTIVE ANTIOXIDANT: EFFECT OF SABINENE IN KETAMINE-INDUCED EXPERIMENTAL SCHIZOPHRENIA IN MICE

Schizophrenia is a serious neuropsychiatric disorder marked by oxidative stress, immune system changes, and neurochemical imbalances. Current treatments are constrained by inconsistent effectiveness and side effects. This study evaluates the neuroprotective effects of sabinene, a monoterpene, in a ketamine-induced schizophrenia mouse model. Male mice (n=9/group) received ketamine (25 mg/kg/day, i.p.) for 14 days to induce schizophrenia-like deficits, followed by treatment with sabinene (5 or 10 mg/kg, p.o.) or risperidone (0.5 mg/kg, p.o.) from days 8-14. Neurochemical analyses assessed oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), malondialdehyde (MDA), and nitrite. This was followed by assays of acetylcholinesterase and levels of cytokines (IL-6 and IL-10) in the prefrontal cortex, striatum hippocampus. Ketamine induced hyperactivity, social withdrawal and memory impairment were reversed by sabinene compared to the ketamine group. Sabinene (10 mg/kg) and risperidone restored SOD, GST, GSH, and CAT levels across regions. The increased MDA and nitrite levels by ketamine were reversed by sabinene in the prefrontal cortex, striatum, and hippocampus compared to the ketamine groups. Sabinene (10 mg/kg) also attenuated acetylcholinesterase in the prefrontal cortex and hippocampus (p < 0.0078). The 5 mg/kg dose showed limited efficacy, indicating dose-dependency. Sabinene’s efficacy, comparable to risperidone, involves enhancement of the cholinergic system and inhibition of oxidative/nitrergic stress, suggesting its potential as a therapeutic agent for schizophrenia by improving cholinergic transmission deficits. Further mechanistic and clinical studies are warranted to optimize sabinene’s therapeutic benefits and antipsychotic potential. Ketamine, Oxidative stress, Schizophrenia, Antioxidants, Sabinene, Acetylcholine.