AMELIORATIVE EFFECTS OF SELECTIVE PDE-10 INHIBITORS AGAINST KETAMINE-MEDIATED SCHIZOPHRENIC OUTCOMES IN MICE

A phosphodiesterase-10 inhibitor, papaverine, protected mice from schizophrenia-like behavioral and brain changes caused by ketamine. Mice given ketamine for 10 days showed increased immobility, altered movement and anxiety-like behavior, reduced social interaction, cognitive impairment, and catalepsy, along with higher oxidative stress and altered acetylcholinesterase activity and brain histology. Both papaverine and the standard antipsychotic clozapine significantly reversed these behavioral, biochemical, and histological abnormalities. The findings suggest papaverine may have neuroprotective potential against schizophrenia-related deficits.

Study at a glance

Abstract

Objectives: Schizophrenia (SCZ) is characterized by significant impairments in perception and cognitive flexibility. Making accurate plans for therapy demands a deeper comprehension of the brain mechanisms behind these disorders. The purpose of our investigation is to analyze the protective effects of papaverine, a phosphodiesterase-10 inhibitor, on ketamine-induced SCZ -like behavioral and biochemical alterations in mice. Methods: For 10 consecutive days, mice were exposed to ketamine (30 mg/kg; i.p.) to develop a SCZ-like phenotype. Various behavioral tests, including social interactions, catalepsy, cognitive impairment (Morris water maze), locomotor and anxiety (open field test), and immobility duration (forced swim test), were assessed. Biochemicals (acetylcholinesterase [AChE] activity, glutathione, and lipid peroxides), and histopathological alterations were also investigated. In this study, papaverine (30 mg/kg; i.p.) and clozapine (7.5 mg/kg p.o.) served as test and standard, respectively. Results were statistically analyzed and “one-way ANOVA” was performed, and Tukey’s multiple comparison test was subsequently applied.” Results: After 28 days of ketamine therapy, significant (p≤0.05) behavioral alterations have been noted, including increased immobility duration, altered locomotor and anxiety-like behaviors, social interactions, cognitive impairment, and catalepsy. Significant alterations in histopathology, AChE activity, and oxidative stress (increased lipid peroxides and lower glutathione) were also observed in mice treated with ketamine. Treatment with clozapine and papaverine considerably (p≤0.05) improved the biochemical changes, behavioral problems, and histological changes. Conclusion: We may conclude that papaverine may have neurodefensive effects against ketamine-induced SCZ in mice based on behavioral, histological, and biochemical observations.