Antipsychotic-induced oxidative stress in rat brain

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Typical and atypical antipsychotics exhibit distinct clinical and behavioral effects.
• Haloperidol (HAL), a typical neuroleptic, primarily antagonizes D(2) dopamine receptors.
• Reactive oxygen species are implicated in the neurotoxic effects of haloperidol.

Purpose of the Study:

• To investigate oxidative damage in rat brains following chronic administration of typical (haloperidol) and atypical (clozapine, olanzapine, aripiprazole) antipsychotics.
• To compare the neurotoxic profiles of different antipsychotic classes regarding oxidative stress markers.

Main Methods:

• Adult male Wistar rats received daily injections of HAL, clozapine (CLO), olanzapine (OLZ), or aripiprazole (ARI) for 28 days.
• Measurements included thiobarbituric acid reactive substances (TBARS) and protein carbonylation in specific brain regions (prefrontal cortex, hippocampus, striatum, cerebral cortex).
• Mitochondrial superoxide levels were also assessed in certain brain areas.

Main Results:

• Haloperidol increased TBARS in the striatum; clozapine and haloperidol increased protein carbonyls in the hippocampus.
• Olanzapine and aripiprazole decreased TBARS in the prefrontal cortex and cerebral cortex, and did not increase protein carbonyls.
• Aripiprazole (20 mg/kg) increased mitochondrial superoxide in the prefrontal cortex and striatum, but not other brain regions or with other drugs.

Conclusions:

• Olanzapine and aripiprazole did not induce the oxidative damage observed with haloperidol and clozapine.
• Atypical antipsychotics olanzapine and aripiprazole appear to have a safer neurotoxic profile concerning oxidative stress compared to typical antipsychotics.
• Findings contribute to understanding the differential neurotoxic mechanisms of antipsychotic drugs.