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

## TL;DR

This study shows that tramadol, a painkiller, can cause brain changes in rats, especially in the cerebrum, which might lead to long-term issues like cognitive and mood problems.

## Contribution

The study provides new evidence of tramadol-induced neurotoxicity in the cerebrum of rats through behavioral, oxidative stress, and histopathological assessments.

## Key findings

- Tramadol caused increased aggression and weight loss in rats, especially at higher doses.
- Mild morphological changes were observed in the cerebrum of tramadol-treated rats.
- Catalase levels were the only oxidative stress marker affected by tramadol treatment.

## Abstract

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.