Neurotoxic Effects of Tramadol Administration on the Cerebellar and Cerebral Cortices of Adult Male Wistar Rats

Background Tramadol, a widely prescribed synthetic opioid, is commonly used for managing moderate to severe pain due to its dual mechanism of action as a μ-opioid receptor agonist and norepinephrine and serotonin reuptake inhibitor. Aim To evaluate the neurotoxic effects of tramadol administration on the cerebellar and cerebral cortices of adult male Wistar rats, focusing on behavioural changes, oxidative stress markers, and histopathological alterations. Materials and methods Twenty adult male Wistar rats were divided into four groups of five rats each: a control group and three treatment groups receiving 25 mg/kg, 50 mg/kg, and 75 mg/kg of tramadol orally, respectively, for 21 days. Physical behaviour was monitored. Oxidative stress markers were assessed. Histological examination of the cerebellum and cerebrum was also carried out. Results The tramadol-treated groups exhibited increased aggression and significant weight loss, particularly at higher doses. Oxidative stress markers showed no changes in the antioxidant enzymes assayed with the exception of catalase. Histopathological examination of the cerebellum showed intact cerebellar layers at the cortex with normal cellular structure and orientations for the control and treated group, while that of the cerebrum revealed mild morphological alterations in the cerebrum of tramadol-treated rats compared to the control group. Conclusion These findings suggest that tramadol exposure can lead to neurotoxic effects in the cerebrum of rats. The observed morphological and histological changes may contribute to the development of long-term adverse effects associated with tramadol use, such as cognitive impairment and mood disorders.