PROTECTIVE EFFECT OF CILOSTAZOL AGAINST KETAMINE-INDUCED BIOCHEMICAL AND BEHAVIORAL PHENOTYPE OF SCHIZOPHRENIA IN MICE

Objective: Schizophrenia (SCZ), a mental illness affecting 1% of the world population, is characterized by extensive structural and functional brain changes. It is brought on by a confluence of psychological, environmental, and hereditary variables. It is frequently coexisted with other diseases, lowering the quality of life and increasing the risk of early death. The objective of this research is to explored the potential of cilostazol (Phosphodiesterase-3 inhibitor) in ketamine (KET)-induced SCZ -like behavioral and biochemical alterations in mice. Methods: In mice, SCZ was induced by injecting KET (30 mg/kg; i.p.) for 10 days in a row. Different behavioral parameters such as immobility time (Forced swim test), locomotor and anxiety (open field test), cognitive dysfunction (Morris water maze), social interactions, and catalepsy were examined. Histopathological and biochemical changes (lipid peroxides, glutathione [GSH], acetylcholinesterase [AChE] activity) were also examined. Cilostazol (25 and 50 mg/kg; p.o.) as a test and clozapine (7.5 mg/kg p.o.), as a standard drug were used in this investigation. Tukey’s multiple comparison test and one-way analysis of variance were used for statistical analysis of all the findings. p<0.050 was regarded as statistically significant. Results: Significant (p<0.05) behavioral changes have been observed following 28 days of KET treatment (increased immobility time, impaired locomotor and anxiety-like behaviors, cognitive dysfunction, social interactions, and catalepsy). Increased oxidative stress (higher lipid peroxides and decreased GSH), AChE activity, and histopathological changes were also noted significantly in KET -treated mice. Cilostazol and clozapine treatment significantly (p<0.05) corrected the histological changes, biochemical alterations, and behavioral problems. Conclusion: As per the behavioral, histopathological, and biochemical outcomes, we can draw a conclusion that cilostazol may provide neurodefensive effects against KET -induced SCZ in mice.