Neuroprotective Effects of Eleveted Dose Vitamin A on the Hippocampus of Adult Male Wistar Rats Exposed to Toxic Doses of Methamphetamine

Abstract

Methamphetamine overstimulates brain regions such as the striatum and hippocampus by increasing neurotransmitter activity, thereby causing neurotoxicity, whereas vitamin A may help protect neurons through anti-inflammatory and neuroprotective effects. This study investigated the neuroprotective effects of an elevated dose of vitamin A on the hippocampus of adult male Wistar rats exposed to toxic doses of methamphetamine (METH). Twenty adult male rats were randomly divided into four groups (n = 5): Group A (control) received feed and water only; Group B received METH at 5 mg/kg at 3-hour intervals within 12 hours; Group C received vitamin A only (2.5 mg/kg); and Group D received the combined treatment of METH (5 mg/kg at 3-hour intervals within 12 hours) and vitamin A (2.5 mg/kg) for 28 days. After the final administration, the animals were sedated and sacrificed; their brains were harvested, fixed in 10% neutral formol saline, and processed for histological examination using haematoxylin and eosin (H&E) staining. Body-weight analysis revealed weight loss in methamphetamine-intoxicated Wistar rats. Methamphetamine increased MDA levels and reduced GSH and SOD levels, indicating oxidative stress. Hippocampus-dependent cognitive performance assessed using the Morris water maze indicated impaired learning after methamphetamine exposure, whereas vitamin A improved cognition and antioxidant status. Histological analysis revealed better-preserved hippocampal architecture in the vitamin A-treated groups than in the METH-only group. Overall, vitamin A provided partial neuroprotection against METH-induced hippocampal toxicity but did not completely reverse the damage.