Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chronic Exposure to Methadone Induces Activated Microglia and Astrocyte and Cell Death in the Cerebellum of Adult Male Rats

Version 1 : Received: 5 March 2022 / Approved: 10 March 2022 / Online: 10 March 2022 (14:22:33 CET)

How to cite: Zamani, N.; Takbiri Osgoei, L.; Aghaei, A.; Hassanian Moghaddam, H.; Zamani, N. Chronic Exposure to Methadone Induces Activated Microglia and Astrocyte and Cell Death in the Cerebellum of Adult Male Rats. Preprints 2022, 2022030153 (doi: 10.20944/preprints202203.0153.v1). Zamani, N.; Takbiri Osgoei, L.; Aghaei, A.; Hassanian Moghaddam, H.; Zamani, N. Chronic Exposure to Methadone Induces Activated Microglia and Astrocyte and Cell Death in the Cerebellum of Adult Male Rats. Preprints 2022, 2022030153 (doi: 10.20944/preprints202203.0153.v1).

Abstract

Background: Methadone is a centrally-acting synthetic opioid analgesic widely used in the methadone maintenance therapy (MMT) programs throughout the world. Considering its neurotoxic effects particularly on the cerebellum, this study aims to address the behavioral and histological alterations in the cerebellar cortex associated with methadone administration. Materials and Methods: 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. The functional and structural changes in the cerebellum were compared to the control group. Results: Our data revealed that treating rats with methadone not only induced cerebellar atrophy, but also prompted the actuation of microgliosis, astrogliosis, and apoptotic biomarkers. We further demonstrated that treating rats with methadone increased complexity of astrocyte processes and decreased complexity of microglia processes. Our result showed that methadone impaired motor coordination and locomotor performance and neuromuscular activity. Additionally, relative gene expression of TNF-α, caspase-3 and RIPK3 increased significantly due to methadone. Conclusions: Our findings suggest that methadone administration has a neurodegenerative effect on the cerebellar cortex via dysregulation of microgliosis, astrogliosis, apoptosis, and neuro-inflammation.

Keywords

Apoptosis; Cerebellum; Methadone; Neuroinflammation

Subject

MEDICINE & PHARMACOLOGY, Behavioral Neuroscience

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