Alzheimer’s and antipsychotics: investigating neuroprotective and behavioral outcomes in rats

Alzheimer’s disease (AD) remains the leading cause of dementia in the elderly, with no definitive cure. Recently, antipsychotic drugs (APDs) have shown effectiveness in managing neuropsychiatric symptoms liked those associated with AD. This study investigated the neurobiological effects of traditional APDs (chlorpromazine and haloperidol) and modern APDs (clozapine and olanzapine) on oxidative stress, neuroinflammation, neuronal injury, and cognitive-behavioral symptoms in an aluminum chloride (AlCl₃)-induced rat model of AD. Sixty adult male rats were divided into ten groups: a saline control, an AlCl₃-only group, and eight groups received AlCl₃ (10 mg/kg/day) for two months, alongside APDs at 1.5 or 3 mg/kg during the second month. At the end of the second month, behavioral responses were examined via the open field test, followed by immunohistopathological and biochemical assessments. A colorimetric spectrophotometer was used to determine the levels of malondialdehyde, nitric oxide, paraoxonase 1, and acetylcholinesterase. Meanwhile, the levels of reduced glutathione, monocyte chemoattractant protein-1, interleukin-1 beta, amyloid-beta peptide, and neuron-specific enolase were determined using an enzyme-linked immunosorbent assay. APDs mitigated AlCl₃-induced AD-like symptoms by improving behavioral deficits and reducing oxidative stress, neuroinflammation, neuronal injury, and acetylcholinesterase activity, with modern types enhancing cognition and behavior, while traditional ones exhibiting stronger antioxidant effects.