Long Term and High Dose Administration of Methylphenidate- Induced Cerebellar Morphological and Functional Damage in Adult Rats

Long Term and High Dose Administration of Methylphenidate- Induced Cerebellar Morphological and Functional Damage in Adult Rats
Amir Raoofi,^1,*
1. Cellular and Molecular Research Center,department of Anatomical Sciences, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
Introduction: Stated in previous studies, physicians are typically prescribing Methylphenidate (MPH), commonly known as Ritalin, for children diagnosed with attention deficit hyperactivity disorder (ADHD). Nevertheless, researchers have not still understood mechanisms of this stimulant medication. Research has also found an association between apoptosis signaling pathway, neurological disorder, as well as treatment targets for neurological diseases. Therefore, the present study investigated effects of 3-week MPH oral (20 mg/kg) administration versus vehicle therapy on cerebellar morphology and function in adult male rats.
Methods: A total number of 30 adult male rats were randomly but equally divided into control and treatment groups. In fact, the treatment group was administered by MPH at doses of 20 mg/kg for 21 days and the control group only received saline solution. At the end of weeks 1, 2, and 3 following drug treatment, rotarod performance test was fulfilled. Once the study ended, tissues of the cerebellum were separated; then, inflammation parameters (i.e. tumor necrosis factor [TNF- α] and interleukin 1 beta [IL-1β]), pro-apoptotic genes (that is, bcl-2-associated X [bax] and caspase-8 proteins), along with histological changes were analyzed.
Results: According to the findings, MPH with the high dose of 20 mg/kg could remarkably enhance the levels of bax and caspase-8 genes compared with those in the control group (p<0.05). It should be noted that treatment with MPH could significantly increase TNF-α and IL-1β levels in isolated cerebellar cells (p<0.05). Moreover, 20 mg/kg of MPH decreased mean volumes of granular layer, white matter, as well as molecular layers. It also reduced the number of Purkinje cells compared with those in control rats. In addition, lower coordination movement was observed in the group receiving MPH.
Conclusion: Data analysis showed that chronic treatment with increased dose of MPH could possibly lead to neuroinflammation and neurodegeneration in the cerebellum of adult rats.
Keywords: Apoptosis, Inflammation, Cerebellum, Rat, MPH, Neurodegeneration