Role of Elevated Dosage of Vitamin A on the Prefrontal Cortex of Adult Male Wistar Rats Exposed to Methamphetamine

Abstract

Methamphetamine (METH), a highly addictive psychostimulant, is known to induce neurotoxicity in brain regions involved in cognitive processing, particularly the prefrontal cortex (PFC). This damage is mediated by oxidative stress, inflammation, and neuronal degeneration. Vitamin A, particularly in its active form, retinoic acid, contributes to brain health by influencing gene expression, neuronal survival, and plasticity. This study investigated the potential protective role of an elevated dose of vitamin A in the prefrontal cortex of adult male Wistar rats exposed to methamphetamine. Twenty rats were randomly divided into four groups (n = 5): Group A (control), Group B (METH only; 5 mg/kg at 3-hour intervals within 12 hours each day), Group C (vitamin A only; 2.5 mg/kg), and Group D (METH, 5 mg/kg at 3-hour intervals within 12 hours each day, plus vitamin A, 2.5 mg/kg). The animals received feed and water, and the treatments were administered orally for 28 consecutive days. After the final administration, the animals were sedated and sacrificed; their brains were harvested, fixed in 10% neutral-buffered formalin, and processed for histological examination using haematoxylin and eosin (H&E) staining. Body-weight, oxidative-stress biomarker, and histological findings indicated that methamphetamine exposure caused weight loss, increased oxidative stress, and severe neuronal damage. However, co-administration of high-dose vitamin A was associated with increased body weight, reduced oxidative stress, and milder neuronal damage. These findings suggest a potential neuroprotective effect of vitamin A against METH-induced damage under the experimental conditions.