Investigating the Toxic Effect of Methadone on the Cerebellar Tissue of Adult Male Rats

The cerebellum is a part of the nervous system that is associated with motor coordination and balance control. Methadone is a centrally-acting synthetic opioid analgesic widely used in methadone maintenance therapy (MMT) programs throughout the world. Unfortunately, the abuse of methadone is currently spreading, and on the other hand, many deaths due to the use of this drug have also been reported. There is still no detailed information about the toxicity of this drug on the nervous system. Therefore, considering its neurotoxic effects, especially on the cerebellum, the aim of this study is to investigate histological changes in the cerebellar cortex associated with methadone administration.

This research is an experimental study. Twenty - four adult male albino rats were randomized into two groups of control and methadone treatment. Methadone was subcutaneously administered (2.5-10 mg/kg) once a day for two consecutive weeks. Stereology was used to evaluate the volume and number of cells in the cerebellar cortex, and immunohistochemistry was used against calbindin to evaluate the number of Purkinje neurons. Data analysis was done with Prism software and independent t-test.

The results of our study showed that administration of methadone decreased the volume of the molecular layer compared to the control group (P < 0.01) (P < 0.017, t = 5.37, Mean ± SEM = 1.429 ± 0.26) (the mean of the control group was 6.05 and the methadone group was 4.62). On the other hand, the number of Purkinje neurons in the methadone group showed a significant decrease compared to the control one (P < 0.05) (P < 0.016, t = 3.291, Mean ± SEM = 2264 ± 687.9) (the mean of the control group was 17826 and the mean of the methadone group was 15562). Our findings also showed that the volume of the granular layer (P < 0.04, t = 2.479, Mean ± SEM = 0.33 ± 0.825) (the mean of the control group was 4.375 and the mean of the methadone group was 3.55) and the volume of the white matter of the cerebellum in the methadone group showed a significant decrease compared to the control group (P < 0.02, t = 3.03, Mean ± SEM = 1.229 ± 0.404) (the mean of the control group was 3.28 and the mean of the methadone group was 2.06). In addition, the number of calbindin- positive neurons showed a significant decrease in the methadone group compared to the control group (P < 0.02, t = 2.68, Mean ± SEM = 2.68 ± 7.2) (the mean of the control group was 20.8 and the methadone group was 13.6).

These findings showed that methadone administration caused damage to the gray and white matter of the cerebellum. The death of Purkinje cells due to methadone can cause disturbances in cerebellar functions. It seems that the administration of methadone should be accompanied by more precautions.