Effects of Risperidone and Aripiprazole Antipsychotic Drugs on Behavioral Changes and the Expression Levels of DRD2, HTR2A, AKT1, and CACNA1C Genes in the Hippocampus of a Ketamine-induced Schizophrenia-like Rat Model

Abstract

Schizophrenia, a severe neuropsychiatric disorder, is characterized by significant impairments in neurological function. The disease includes a spectrum of symptoms that are divided into four main categories: positive, negative, cognitive, and mood symptoms. In this study, 32 male Wistar rats, approximately 10 to 12 weeks old, were randomly separated into four groups: vehicle (saline), ketamine (30 mg/kg), aripiprazole (0.75 mg/kg), and risperidone (1 mg/kg). Twenty-four hours following the final ketamine or saline administration, social interaction test (SIT), open field test (OFT), novel object recognition (NOR), and elevated plus-maze (EPM) were performed on the animals. Hippocampal tissue was used for molecular analysis using Real-Time PCR technique. Behavioral tests revealed that both risperidone and aripiprazole reduced anxiety-like behaviors and enhanced cognitive discrimination. At the molecular level, hippocampal expression of DRD2 and HTR2A did not differ significantly across groups. However, the ketamine-treated group exhibited elevated AKT1 expression relative to the vehicle group, whereas risperidone administration downregulated AKT1 compared to the ketamine group. Notably, CACNA1C expression was upregulated in the aripiprazole group compared to both the ketamine and vehicle groups. The findings of this study showed that the antipsychotic drugs risperidone and aripiprazole have the ability to moderately alleviate cognitive deficits in rats. The results also indicated that this treatment may affect the gene expression of AKT1, and CACNA1C genes.

Graphical Abstract