Background Schizophrenia is a complex mental disorder characterized by recurring episodes of psychosis, which disrupt an individual’s perception of reality. Symptoms often emerge gradually in early adulthood and can persist throughout life. Diagnosing schizophrenia involves thorough assessments of behavior, psychiatric history, and input from those close to the individual. The disorder’s heterogeneity complicates understanding its causes and mechanisms. Recent research has spotlighted ketamine, an NMDA receptor antagonist, as a crucial tool for studying psychosis. In this study, we induced schizophrenia-like conditions in rats using ketamine administered to the prefrontal cortex, confirmed through behavioral and neurochemical evaluations. We found that dysregulation of neurotransmitters such as dopamine (DA), serotonin, and glutamate plays a significant role in psychosis development. Experimental Approach Resveratrol (RSV) exhibited antioxidant properties and positively influenced DA levels, while tetrabenazine (TBZ) targeted dysregulated DA neurotransmission. Both compounds showed promise in alleviating behavioral deficits associated with ketamine-induced psychosis. Additionally, they may help mitigate neuroinflammatory changes linked to oxidative stress in the brain. Conclusion This research underscores the potential of RSV and TBZ as therapeutic agents for restoring neurotransmission disrupted by psychosis, offering new avenues for managing schizophrenia effectively.