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

Tihomir Stojković1, Nevena V Radonjić, Milica Velimirović

  • 1Institute of Clinical and Medical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|June 28, 2012
PubMed

Insights

Risperidone treatment reversed key oxidative stress markers in rats exposed to phencyclidine (PCP) during development. This suggests potential therapeutic benefits for schizophrenia by restoring glutathione levels and antioxidant enzyme function.

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.

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