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- 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, 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-α and IL-1β 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.

中文翻译：

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长期服用大剂量哌醋甲酯诱导成年大鼠小脑形态和功能损伤

背景和目的 先前的研究表明，医生通常会为诊断出患有注意力缺陷多动障碍 (ADHD) 的儿童开哌甲酯 (MPH)，通常称为利他林。尽管如此，研究人员仍然不了解这种兴奋剂药物的机制。研究还发现细胞凋亡信号通路、神经系统疾病以及神经系统疾病的治疗靶点之间存在关联。因此，本研究调查了 3 周口服利他林 (20 mg/kg) 给药与载体疗法对成年雄性大鼠小脑形态和功能的影响。材料与方法 将30只成年雄性大鼠随机等分为对照组和治疗组。实际上，治疗组给予利他林20mg/kg 21天，对照组仅给予生理盐水。在药物治疗后的第 1、2 和 3 周结束时，完成了旋转棒性能测试。研究结束后，小脑组织被分离；然后，炎症参数（即肿瘤坏死因子 [TNF-α] 和白细胞介素 1β [IL-1β]）、促凋亡基因（即 bcl-2 相关 X [bax] 和 caspase-8 蛋白），以及与组织学变化进行分析。结果根据研究结果，与对照组相比，20 mg/kg高剂量利他林可显着提高bax和caspase-8基因水平（p < 0.05）。应该注意的是，用利他林治疗可以显着增加分离的小脑细胞中的 TNF-α 和 IL-1β 水平（p < 0.05）。而且，20 mg/kg 的利他林降低了颗粒层、白质和分子层的平均体积。与对照大鼠相比，它还减少了浦肯野细胞的数量。此外，在接受利他林的组中观察到较低的协调运动。结论 数据分析表明，长期增加利他林剂量治疗可能导致成年大鼠小脑的神经炎症和神经变性。