Risperidone reverses phencyclidine induced decrease in glutathione levels and alterations of antioxidant defense in...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Perinatal phencyclidine (PCP) administration in rats models schizophrenia, a condition linked to redox dysregulation.
• Previous studies showed reduced glutathione (GSH) and imbalanced antioxidant enzymes in PCP-treated rats.
• Antioxidant defense mechanisms are crucial in brain function and disease pathology.

Purpose of the Study:

• To investigate if chronic risperidone treatment can reverse oxidative stress markers in a rat model of schizophrenia.
• To assess the impact of risperidone on glutathione levels and antioxidant enzyme activities in PCP-exposed rats.
• To evaluate risperidone's effect on lipid peroxidation in specific brain regions.

Main Methods:

• Wistar rats received perinatal PCP or saline, followed by chronic risperidone treatment from postnatal day 35 to 100.
• GSH levels, activities of γ-glutamate cysteine ligase (GCL), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) were measured.
• Lipid peroxide concentrations were determined in various brain structures.

Main Results:

• Risperidone normalized decreased GSH levels and GCL activity in the cortex and hippocampus.
• The drug reversed PCP-induced alterations in GPx and GR activities in most brain regions.
• Risperidone decreased SOD activity in both control and PCP groups and reduced elevated lipid peroxides in the hippocampus and thalamus.

Conclusions:

• Chronic risperidone treatment effectively restores GSH levels and reverses antioxidant defense alterations in perinatally PCP-treated rats.
• These findings highlight risperidone's potential role in mitigating PCP-induced oxidative stress relevant to schizophrenia.
• Further research is needed to fully understand risperidone's influence on oxidative stress in schizophrenia.