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

Abstract

ABSTRACT

Objectives: Schizophrenia is characterised 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 objective of our investigation is to evaluate the protective effects of papaverine, a phosphodiesterase-10 inhibitor, on ketamine-induced schizophrenia-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 schizophrenia 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, clozapine (7.5 mg/kg p.o.) was used as a conventional medication and papaverine (15 and 30 mg/kg; i.p.) as a test. Results were statistically analyzed by applying one-way ANOVA, followed by Tukey's multiple comparison test.

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 schizophrenia in mice based on behavioral, histological, and biochemical observations.