Long-term administration of high-dose methylphenidate-induced cerebellar morphology and function damage in adult rats

Background and Aim: 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 Ritalin oral (20 mg/kg) administration versus vehicle therapy on cerebellar morphology and function in adult male rats. Materials and 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 Ritalin at doses of 20 mg/kg for 21 days and the control group only received saline. 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- alpha] and interleukin 1 beta [IL-1 beta]), 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, Ritalin 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 Ritalin could significantly increase TNF-alpha and IL-1 beta levels in isolated cerebellar cells (p < 0.05). Moreover, 20 mg/kg of Ritalin 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 Ritalin. Conclusion: Data analysis showed that chronic treatment with increased dose of Ritalin could possibly lead to neuroinflammation and neurodegeneration in the cerebellum of adult rats.