The protective effect of olanzapine on ketamine induced cognitive deficit and increased NR1 expression in rat model of schizophrenia

xlomafota13 shared this article with you from Inoreader The protective effect of olanzapine on ketamine induced cognitive deficit and increased NR1 expression in rat model of schizophrenia Via International Journal of Physiology, Pathophysiology and Pharmacology Int J Physiol Pathophysiol Pharmacol. 2021 Apr 15;13(2):22-35. eCollection 2021. ABSTRACT BACKGROUND: Impaired cognitive flexibility is the core manifestation of schizophrenia (SZ). Previous literature raised a claim against the effect of atypical antipsychotic drugs (AAD) on cognitive and executive functions whose cause needs further investigation. Attention set-shifting task (ASST) tests the prefrontal cortex's (PFC) executive and flexibility functions. GOALS: To examine Olanzapine (OLZ) effect on ASST, expression of N-methyl-D-aspartate receptor 1 (NMDR-NR1) in prefrontal cortex (PFC), and metabolic comorbidity in ketamine (KET) model of SZ. METHODS: Sixty-two male rats were divided into three groups: 8 for ASST and 30 for open field, ELISA and immunohistochemistry sub-chronic study, and 24 for regular serological and histopathological examination. Rats treated with V: vehicle; K: KET and KO: OLZ plus KET. RESULTS: KET caused significant increase in time, trials, and errors to reach criterion. OLZ co-administration reversed effects of KET in ASST with no reduction of locomotor activity. OLZ normalized KET-induced rise of NR1 expression and protected against KET-induced degenerative changes in hippocampus and PFC. Significant increase in serum liver enzymes, total bilirubin, and lipids with chronic compared to sub-chronic OLZ administration. In contrast, insignificant difference between sub-chronic OLZ and vehicle was found. CONCLUSIONS: Current study demonstrated the efficacy of OLZ to reverse KET-induced cognitive deficits in ASST with neither reduction in NR1 expression in PFC nor metabolic malfunction in the sub-chronic study. It also showed the protective effect of OLZ on KET induced neuronal degeneration and necrosis. We suggest that chronic OLZ treatment-induced-metabolic malfunction might be the cause of time-dependent cognitive deterioration. PMID:34093963 | PMC:PMC8166812 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.